**1. Introduction**

The gas disaster is one of the major disasters that threaten coal mine safety production. With the development of coal resources gradually extending to the depths, the difficulty of gas control is increasing. Borehole drainage is the basic gas control measure. At present, gas pre-drainage mainly includes the borehole drilling in the bedding coal seam and the penetrating borehole in the bottom roadway, which can penetrate the coal seam so that the gas easily flows into the boreholes along the bedding plane, which can effectively reduce the gas content in the coal seam [1–4]. Buried pipe drainage, high-level drilling, and roof directional drilling are mainly used for gas control in the goaf during mining. Because the

**Citation:** Wang, Z.; Yang, X.; Wang, G.; Gong, H. Study on Instability Characteristics of the Directional Borehole on the Coal-Seam Roof: A Case Study of the Tingnan Coal Mine. *Processes* **2023**, *11*, 1675. https:// doi.org/10.3390/pr11061675

Academic Editor: Raymond Cecil Everson

Received: 13 April 2023 Revised: 11 May 2023 Accepted: 14 May 2023 Published: 31 May 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

roof directional borehole is located in the fracture zone of the coal seam, where the horizon is high and less affected by mining disturbance, the borehole and gas drainage life cycle is long, which can effectively solve the problem of gas overflow in the upper corner of the goaf [5–8].

However, the openings of roof directional boreholes are often located in the coal seam, and they have to pass through mudstone and sandstone before entering the fracture zone. Due to the large diameter of the borehole (typically around 160 mm), the boreholes are susceptible to loss of stability resulting in deformation and collapse. Therefore, the stability of the directional borehole on the roof through the strata directly affects its drainage effect. Borehole diameter, lithology, and other parameters are important parameters affecting borehole stability [9,10].

Research on the influencing factors of borehole stability and borehole failure modes in the bedded coal seam has been conducted by scholars at home and abroad. The influencing factors of borehole stability mainly include rock strength, gas pressure, stress and strain, burial depth, lateral pressure coefficient, and anisotropic permeability [11–14]. Yang et al. [15] indicated that rock mechanics is the main theoretical basis for ensuring good stability, sand production, or casing damage. Karatela et al. [12] investigated the stability of boreholes in fractured rock using the discrete element method. The results show that the stability of boreholes depends largely on the strength of the rock. The tensile and shear failure of the borehole increases with increasing fluid velocity and pore pressure. Ding et al. [16] found that the large difference in permeability of rock layers around the borehole would lead to the change in stress state, damage area, collapse pressure, and fracture pressure around the borehole. Zhao et al. [17] studied the instability characteristics of the borehole under steady vertical load using the gas drainage borehole collapse dynamic monitoring devices. The attenuation of the borehole circumferential strain is an important symbol for the prediction and warning of borehole instability and collapse. A borehole may be damaged resulting from the integrated effect of stratigraphic and structural factors. Katanov et al. [18] proposed a model based on neural simulation to analyze the deformation of rock layers with different strength characteristics. Ma et al. [19] solved the problem of severe borehole deviation in coal mine gas drainage by summarizing the borehole deviation law and improving the precision directional drilling tool. Dychkovsky et al. [20] simulated the influence of geological faults on the stress and deformation state of rock mass by FLAC 5.00 and established a three-dimensional network visualization by computer simulation results and data interpolation method. The research shows that in the Lviv-Volyn coal basin, the geological fault of up to 3 m distance has a great influence on the stress and deformation state of the rock mass. Based on the parameters of the geo-mechanical model developed and confirmed, Petlovanyil et al. [21] have determined the reasonable range of inclination angle and key parameters of the radius of curvature when using underground gasification technology to develop thin coal seams. Zhang et al. [22] numerically simulated the deformation characteristics of boreholes with different burial depths, and the results showed that the deeper the burial depth, the more obvious the deformation. The form of instability and failure was the collapse of the upper part, and the fracture of the left and right sides formed the fracture area. Qu et al. [23] found that the stability of coal seam borehole was affected by the time lag effect based on field tests and numerical simulation; they found that the change of pore pressure was the main factor affecting the time lag effect, and the rich cleat was the internal factor. Niu et al. [24,25] studied the monitoring and evaluation of borehole stability through experiments and simulations, proposed an index to calculate the degree of borehole damage based on the residual area, and fitted the functional equation between the relative pressure of the sensor (the difference between the real-time pressure of the sensor and the coupling pressure of the borehole wall) and the degree of borehole damage. Combined with the amount of gas extracted, it was verified that the borehole deformation first increased and then became stable with time, and then increased and then decreased with depth. Zhang et al. [26] established the gas migration channel zoning model and determined the parameters of the optimal directional long borehole in

the working face by using UDEC and COMSOL software. Xu et al. [27] found that when the borehole is shallow, the friction resistance between the drill pipe and the borehole wall increases linearly. With the increase of borehole depth, the friction resistance gradually develops into an exponential relationship. In addition, Liu et al. [28] concluded that the effective drainage radius of a directional long drilling hole has an exponential relationship with the distance from the drilling opening. Yuan et al. [29,30] conducted the combined drilling method of curtain grouting in underground deep wells, which can significantly reduce the risk of water inrush in deep mining with complex hydrogeological conditions. A mathematical model to describe the unstable pressure dynamics in stress-sensitive coalbed methane reservoirs was proposed by Wang et al. [31]. Wang et al. [32] proposed the gradient recognition and memory-cutting method for the continuous advancement of non-uniform coal seams, such as coal seams with folded structures on long-arm working-face.

Moreover, scholars have conducted a great number of field tests and research on a series of borehole protection technologies, such as borehole reinforcement, regional solidification, and screen protection. Xue et al. [33] found that increasing the casing strength and thickness can effectively control the borehole instability and greatly improve the gas extraction effect through field tests. To improve the stability of the borehole. Zhai et al. [34] conducted research on the technology of screen pipe protection. By comparing the maximum AE event technology and energy dissipation rate, it was found that the screen pipe can effectively resist external stress disturbance, prevent hole collapse, and improve the drainage effect of the borehole. Di et al. [35] proposed the regional solidification pore formation method for soft coal seams, which can solidify the strength of the rock surrounding the borehole and improve the pore formation rate. Qi et al. [36] tested the full-hole deep screen mesh tube drainage technology to solve the problem of internal collapse and negative pressure loss of deep coal seam drainage boreholes, which can effectively control the collapse and deformation of boreholes and reduce the negative pressure loss. Compared with conventional drainage, after 90 days, the gas drainage concentration increased by 101% and the gas flow increased by 97%, so the gas drainage rate increased significantly. Li et al. [37] proposed to integrate the technology of borehole digging, protection, and sealing in the construction of the borehole site, so as to strengthen the stability of the borehole and solve the problems of difficult borehole formation, poor drainage effect and high danger of coal seam explosion in soft coal seams.

Currently, the research on borehole stability mainly focuses on the surrounding rock stress, burial depth, lateral pressure coefficient, anisotropic permeability, and other influencing factors, and the failure characteristics of the borehole in the bedding coal seam, while the research on the stability and borehole protection technology of roof directional long borehole is still lacking. Compared with the traditional high-position alley gas extraction technology, the roof directional long borehole has the advantages of a short construction period, low investment, and long extraction period. Therefore, the stability of the roofdirectional long borehole with different lithology and borehole diameters was analyzed by numerical simulation in this paper. The compression experiments were carried out to study the protective effect of different internal support structures in the directional borehole, which is beneficial to realize the effective hole formation of the directional long borehole on the roof and high-efficiency gas extraction in the goaf treatment of the coal mine face. This paper will provide some guidance for the popularization and application of directional long boreholes on the roof technology, and also gradually realize the "replacing alley with borehole" in goaf gas treatment. The rest of this study is organized as follows. Section 2 analyzes the deformation characteristics of boreholes under different coal and rock conditions, and simulates the stress, strain, and plastic deformation of rocks around boreholes with different diameters. In Section 3, the experiment on the influence of the internal support hole protection tube on the stability of the hole wall was carried out. Section 4 analyzes the mechanism of numerical simulation and laboratory experiment results. Finally, the conclusions are presented in Section 5.

#### **2. Numerical Simulation of the Borehole Stability**

Lithology, borehole diameter, and borehole protection tubing have a great influence on the stability of the borehole; for example, the strength of the rock will affect the rate of hole formation and the durability of the borehole. The larger the diameter of the borehole, the closer it is to the uniaxial compressive strength of the rock and the easier it is to destroy the stability of the borehole in the rock formation. The shear strength of the casing is also closely related to the effectiveness of the casing [38–40]. Therefore, this section takes the 208-working face of Tingnan Coal Mine in Xianyang, Shaanxi Province, China as an object to conduct numerical simulation research to analyze the influence of lithology, borehole diameter, borehole protection pipe, and other factors on borehole stability. Tingnan Mine Field is mainly covered by Quaternary loess and Tertiary red soil, and the Lower Cretaceous Luohe Formation is exposed in major valleys along the Heihe River and Jinghe River. The strata in the minefield of Tingnan Coal Mine are, from top to bottom, Holocene (Q4), Upper Pleistocene Malan Formation (Q3), Quaternary-Middle Pleistocene Lishi Formation (Q2), Huachi Formation (K1h), Luohe Formation (K11), Lower Cretaceous Yijun Formation (K1y), Anding Formation (J2a), Zhiluo Formation (J2z) and Middle Cretaceous Yanan Formation. The Jurassic Yan'an Formation is a coal-bearing layer, and the Triassic Hujiahe Formation is a direct or indirect sedimentary basement. The surface and overlying strata are basically the same, and the aquifer of the Luohe Formation is in the upper part. The minefield is located in the middle part of the anticline (Lujia–Xiaolingtai), and the stratum in the middle is close to the level. The terrain in the south wing is gentler than that in the north wing, and the dip angle in the north wing is 4◦~6◦. The back of the syncline is Mengcun, which is connected with the north wing of the anticline from Lujia to Xiaolingtai. The strike of the layer is N 20◦ E and the dip angle is about 2◦. The north wing crosses the Great Buddha Temple to the south and the occurrence of the southeast corner of the layer changes. The anticline structure affects the change of layer thickness, coal seam thickness, and occurrence in the minefield. Tingnan coal mine is a high-gas mine, and the 4# coal seams belong to the type II spontaneous combustion coal seams, and the coal dust is explosive. The coal seam thickness of the 208-working face varies greatly, with the average coal seam thickness being 11.5 sm. The base roof of the working face is coarse-grained sandstone, which is grey and mainly composed of quartz and feldspar. The immediate roof is mudstone, dark grey and lumpy, containing a large number of plant fossils and locally a small number of calcite veins. The direct floor is aluminum mudstone, light grey, dense, and contains plant root fossils. The base is fine-grained sandstone, light grey, chestnut, and hard, with sandy muddy breccias. The 208-working face is located in the west wing of the second panel, with a total length of 2527 m. The description of formation lithology characteristics is shown in Table 1.

**Table 1.** The description of formation lithology in 208 working-face.


*Article* **On the Impacts of Pre-Heated Natural Gas Injection in Blast Furnaces**

**Tyamo Okosun 1, Samuel Nielson 1, John D'Alessio 2, Shamik Ray 2, Stuart Street 3 and Chenn Zhou 1,\***

Received: 29 May 2020; Accepted: 28 June 2020; Published: 1 July 2020

**Abstract:** During recent years, there has been great interest in exploring the potential for high-rate natural gas (NG) injection in North American blast furnaces (BFs) due to the fuel's relatively low cost, operational advantages, and reduced carbon footprint. However, it is well documented that increasing NG injection rates results in declining raceway flame temperatures (a quenching effect on the furnace, so to speak), with the end result of a functional limit on the maximum injection rate that can be used while maintaining stable operation. Computational fluid dynamics (CFD) models of the BF raceway and shaft regions developed by Purdue University Northwest's (PNW) Center for Innovation through Visualization and Simulation (CIVS) have been applied to simulate multi-phase reacting flow in industry blast furnaces with the aim of exploring the use of pre-heated NG as a method of widening the BF operating window. Simulations predicted that pre-heated NG injection could increase the flow of sensible heat into the BF and promote complete gas combustion through increased injection velocity and improved turbulent mixing. Modeling also indicated that the quenching effects of a 15% increase in NG injection rate could be countered by a 300K NG pre-heat. This scenario maintained furnace raceway flame temperatures and top gas temperatures at levels similar to those observed in baseline (stable) operation, while reducing coke rate by 6.3%.

**Keywords:** blast furnace; natural gas; fuel injection; computational fluid dynamics; numerical simulation; combustion; RAFT


Patients who have undergone surgical shortening of the vagina, radiation therapy of the pelvis or brachy-therapy should be informed about the available treatment options for vaginal strictures or adhesions to preserve the patient's ability for cohabitation. These include the use of vaginal dilators or bepanthen tampons which can be combined with oestrogen-containing lotions or lubricants. Treatment can be initiated four to six weeks after therapy (GCP Guideline on diagnosis and therapy of cervical cancer 2008, in German). It is important to use the vaginal dilators regularly (e.g. Dilator Set®), even if the patient is not in

Sexuality After Ovarian Cancer Therapy 323

[1] Aerts L, Enzlin P, Verhaeghe J et al. Sexual and psychological functioning in women

[2] Arden-Close E, Gidron Y, Moss-Morris R. Psychological distress and its correlates in

[3] Bhatti Z, Salek M, Finlay A. Chronic diseases influence major life changing decisions: a new domain in quality of life research. J R Soc Med. 2011 Jun;104(6):241-50. [4] Buster JE, Kingsberg SA, Aguirre O et al. Testosterone patch for low sexual desire in

[5] Boehmer U, Potter J, Bowen DJ. Sexual functioning after cancer in sexual minority

[6] Bordeleau L, Pritchard KI, Loprinzi CL, Ennis M, Jugovic O, Warr D, Haq R, Goodwin

[7] Brähler E, Unger U. Sexual activity in advanced age in the context of gender, family

[8] Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of

[11] Carter J, Chi DS, Brown CL, Abu-Rustum NR, Sonoda Y, Aghajanian C, Levine DA,

[12] Corney RH, Crowther ME, Everett H et al. Psychosexual dysfunction in women with

[13] Curry C, Cossich T, Matthews JP et al. Uptake of psychosocial referrals in an outpatient

[14] Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD,

platinum era: a meta-analysis. J Clin Oncol. 2002 Mar 1;20(5):1248-59. [9] Cadron I, Leunen K, Van Gorp T, Amant F, Neven P, Vergote I. Management of borderline ovarian neoplasms. J Clin Oncol. 2007 Jul 10;25(20):2928-37. Review. [10] Carter J, Goldfrank D, Schover LR. J Sex Med. Simple strategies for vaginal health

after pelvic surgery for gynaecological cancer. European journal of gynaecological

ovarian cancer: a systematic review. Psychooncology. 2008 Nov;17(11):1061-72.

surgically menopausal women: a randomized trial. Obstet Gynecol 2005; 105: 944-

PJ. Multicenter, randomized, cross-over clinical trial of venlafaxine versus gabapentin for the management of hot flashes in breast cancer survivors. J Clin

status and personality aspects-results of a representative survey. Z Gerontol. 1994

maximal cytoreductive surgery for advanced ovarian carcinoma during the

promotion in cancer survivors. 2011 Feb;8(2):549-59. doi: 10.1111/j.1743-

Baser RE, Raviv L, Barakat RR. Cancer-related infertility in survivorship. Int J

gynaecological cancer following radical pelvic surgery. British journal of obstetrics

cancer setting: improving service accessibility via the referral process. Support Care

Hirschberg AL, Rodenberg C, Pack S, Koch H, Moufarege A, Studd J; APHRODITE Study Team. Testosterone for low libido in postmenopausal women not taking

**8. References**

Review.

952.

oncology. 2009;30: 652-6.

Mar-Apr;27(2):110-5.

women. Cancer J. 2009 Jan-Feb;15(1):65-9.

6109.2010.01988.x. Epub 2010 Aug 16.

and gynaecology. 1993;100: 73-8.

Cancer. 2002;10: 549-55.

Gynecol Cancer. 2010 Jan;20(1):2-8. Review.

estrogen. N Engl J Med. 2008 Nov 6;359(19):2005-17.

Oncol. 2010 Dec 10;28(35):5147-52. Epub 2010 Nov 8.

a relationship, because dilatation becomes increasingly difficult with time. Accompanying pelvic floor muscle training can be recommended and results in gain over muscle identification, control and strength (Derzko et al. 2007).

### **6. Conclusion**

The potential impact of ovarian cancer therapy such as surgery, chemotherapy or even radiation therapy on sexual function and fertility needs to be discussed with each patient. Even for women in a palliative setting, sexuality and intimacy should be an issue.

Impaired sexual function after treatment of ovarian cancer is a common problem and represents a significant limitation of quality of life. While for younger patients infertility and early postmenopausal symptoms may be of major concern, postmenopausal women might consider the loss of the remaining androgen function of the ovaries as most striking. The significance of radical pelvic and para-aortic lymphadenectomy for sexual function remains unclear.

Local or systemic oestrogen therapy subsequent to treatment of ovarian cancer is considered an adequate treatment of postmenopausal symptoms. Apart from symptomatic therapy, physical interventions (e.g. physiotherapy) and physical activity should be included as supportive actions. For patients with an underlying depressive condition an antidepressive medication should be taken into account, even if only for a limited time.

Health care providers have a model function when discussing therapy-induced changes of sexual function and should regard sexuality as an essential element of quality of life. Therefore, the possible treatment side effects, including therapeutic or preventive options, and the quality of life after cancer must be discussed with the patient prior to therapy initiation. By understanding that sexuality is an important and normal aspect of life and not a "luxury issue" even for patients with a non-curable disease, treating physicians can support their patients and help them to maintain a good or at least acceptable quality of life.

### **7. GCP guidelines**

### **8. References**

322 Ovarian Cancer – Clinical and Therapeutic Perspectives

a relationship, because dilatation becomes increasingly difficult with time. Accompanying pelvic floor muscle training can be recommended and results in gain over muscle identification, control and strength (Derzko et al. 2007).

Impaired sexual function after treatment of ovarian cancer is a common problem and represents a significant limitation of quality of life. While for younger patients infertility and early postmenopausal symptoms may be of major concern, postmenopausal women might consider the loss of the remaining androgen function of the ovaries as most striking. The significance of radical pelvic and para-aortic lymphadenectomy for sexual function remains

Local or systemic oestrogen therapy subsequent to treatment of ovarian cancer is considered an adequate treatment of postmenopausal symptoms. Apart from symptomatic therapy, physical interventions (e.g. physiotherapy) and physical activity should be included as supportive actions. For patients with an underlying depressive condition an antidepressive

Health care providers have a model function when discussing therapy-induced changes of sexual function and should regard sexuality as an essential element of quality of life. Therefore, the possible treatment side effects, including therapeutic or preventive options, and the quality of life after cancer must be discussed with the patient prior to therapy initiation. By understanding that sexuality is an important and normal aspect of life and not a "luxury issue" even for patients with a non-curable disease, treating physicians can support their patients and help them to maintain a good or at least acceptable quality of

1. Interdisciplinary guideline of the German Cancer society and the German Society of Gynecology and Obstetrics on diagnosis and therapy of malignant ovarian tumors. In

2. Interdisciplinary guideline of the German Cancer society and the German Society of Gynecology and Obstetrics on diagnosis and therapy of cervical cancer. In German,

3. Interdisciplinary guideline of the German Osteoporosis Society on prophylaxis, diagnosis and therapy of osteoporosis. In German, 2009.

4. Interdisciplinary guideline of the German Society of Gynecology and Obstetrics on hormone therapy in peri- and postmenopausal women. In German, 2009.

German, 2007. www.awmf.org/leitlinien/detail/ll/032-035.html

2008. www.awmf.org/leitlinien/detail/ll/032-033.html

ww.awmf.org/leitlinien/detail/ll/034-003.html

ww.awmf.org/leitlinien/detail/ll/ 015-062.html

discussed.

unclear.

life.

**7. GCP guidelines**

**6. Conclusion**

Sexuality After Ovarian Cancer Therapy 325

[31] Madeb R, Golijanin D, Knopf J, Vicente I, Erturk E, Patel HR, Joseph JV. Patient-

[33] McGregor BA, Carver CS, Antoni MH, et al. Distress and internalized homophobia

[34] Michaelson-Cohen R, Beller U. Managing menopausal symptoms after gynecological

[35] Mørch LS, Løkkegaard E, Andreasen AH, Krüger-Kjaer S, Lidegaard O. Hormone

[36] Oskay-Oezcelik G, Neubert S, Munstedt K, Liebrich K, Hanker LC, Lorenz R,

[37] Pachman DR, Jones JM, Loprinzi CL. Management of menopause-associated vasomotor

[38] Passik SD, Dugan W, McDonald MV et al. Oncologists' recognition of depression in

[39] Raboch J, Boudnik V, Raboch Jr J. Sex life following hysterectomy. Geburtsh

[40] Reid DM. Prevention of osteoporosis after breast cancer. Maturitas. 2009 Sep 20;64(1):4-

[41] Sadovsky R, Basson R, Krychman M et al. Cancer and sexual problems. The journal of

[42] Shifren JL, Braunstein GD, Simon JA et al. Transdermal testosterone treatment in

[43] Sideras K, Loprinzi CL. Nonhormonal management of hot flashes for women on risk

[44] Sitruk-Ware R. Estrogen therapy during menopause. Practical treatment

[45] Stead ML, Brown JM, Fallowfield L, Selby P. Lack of communication between

[46] Taylor C. Predictors of sexual functioning in ovarian-cancer patients. J of Clin Oncol

[47] Vitrano V, Catania V, Mercadante S. Sexuality in patients with advanced cancer: a

care unit. Am J Hosp Palliat Care. 2011 May;28(3):198-202.

reduction therapy. J Natl Compr Canc Netw. 2010 Oct;8(10):1171-9.

women with impaired sexual function after oophorectomy.  Br J

prospective study in a population admitted to an acute pain relief and palliative

sparing radical prostatectomy. JSLS. 2007 Oct-Dec;11(4):443-8. Review. [32] Mascarenhas C, Lambe M, Bellocco R, Bergfeldt K, Riman T, Persson I, Weiderpass E.

ovarian cancer survival. Int J Cancer. 2006 Dec 15;119(12):2907-15.

cancer. Curr Opin Oncol. 2009 Jul 7. [Epub ahead of print].

Gynaecological Oncology (NOGGO). ASCO 2010.

their patients with cancer. J Clin Oncol. 1998;16: 1594-600.

Womens Health. 2010 Aug 9;2:123-35.

 Drugs 1990; 39: 203–217.

8. Epub 2009 Aug 25.

Cancer 2003; 88: 666–671

2004; 22: 881–889.

682–688

therapy and ovarian cancer. JAMA. 2009 Jul 15;302(3):298-305.

2001;25:1–9.

reported validated functional outcome after extraperitoneal robotic-assisted nerve-

Use of hormone replacement therapy before and after ovarian cancer diagnosis and

among lesbian women treated for early stage breast cancer. Psychol Women Quart.

Wimberger P, Mahner S, Hindenburg HJ, Sehouli J. What do primary and recurrent ovarian cancer (OC) patients expect from their doctors? Final results of a german survey in 676 patients. A Study of The North-Eastern German Society of

symptoms: Current treatment options, challenges and future directions. Int J

[15] Derzko C, Elliott S, Lam W. Management of sexual dysfunction in postmenopausal

[16] Edmondson RJ, Monaghan JM. The epidemiology of ovarian cancer. Int J Gynecol

[17] Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in

[18] Gershenson DM. Management of ovarian germ cell tumors. J Clin Oncol 2007; 25: 2938–

[19] Glantz MJ, Chamberlain MC, Liu Q, Hsieh CC, Edwards KR, Van Horn A, Recht L.

[20] Grzankowski KS, Carney M. Quality of life in ovarian cancer. Cancer Control. 2011

[21] Gupta P, Sturdee DW, Palin SL, et al. Menopausal symptoms in women treated for

[22] Gupta P, Ozel B, Stanczyk FZ, Felix JC, Mishell DR Jr. The effect of transdermal and

[23] Hall E, Frey BN, Soares CN. Non-hormonal treatment strategies for vasomotor symptoms: a critical review. Drugs. 2011 Feb 12;71(3):287-304. Review. [24] Hanker LC, Kaufmann M. Problematik des Ovarialkarzinoms: oft zu spät erkannt, oft

[25] Hasenburg A, Amant F, Aerts L, Pascal A, Achimas-Cadariu P, Kesic V. Psycho-

[26] Hasenburg A, Gabriel B, Einig E-M. Sexualität nach Therapie eines Ovarialkarzinoms.

[27] Henriksson L, Stjernquist M, Boquist L et al. A one year multi-center study of efficacy

[28] Janda M, Obermair A, Cella D et al. Vulvar cancer patients' quality of life: a qualitative

[29] Jefferies H, Groves J. In: Gynecologic Cancer: Controversies in Management. Edited by

[30] Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-

gynecological cancer. Int J Gynecol Cancer 2011, accepted.

2007 Dec;14 Suppl 1:S20-40.

2007 May 22.

Jan;18(1):52-8. Review.

2943.

Cancer. 2001 Nov-Dec;11(6):423-9. Review.

medical illness. Cancer. 2009 Nov 15;115(22):5237-42.

on quality of life. Climacteric 2006;9(1):49–58.

Menopause. 2008 Jan-Feb;15(1):94-7.

Geburtsh Frauenheilk 2008; 68: 994-997.

assessment. Int J Gynecol Cancer. 2004;14: 875-81.

Obstet Gynecol 1996; 174: 85–92.

443-07142-X.

Apr;61(2):133-4.

untertherapiert. Gyn (15) 2010.

breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol.

postmenopausal women. J Clin Endocrinol Metab. 2007 Aug;92(8):3040-3. Epub

Gender disparity in the rate of partner abandonment in patients with serious

breast cancer: the prevalence and severity of symptoms and their perceived effects

vaginal estrogen therapy on markers of postmenopausal estrogen status.

Oncology: Structure and profiles of European centres treating patients with

and safety of a continuous, low dose estradiol releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Am J

David Gershenson, McGuire and Gore von Churchill Livingstone. 2004, ISBN 0-

Oct;60(5):277-300. Epub 2010 Jul 7. Erratum in: CA Cancer J Clin. 2011 Mar-

**17**

*1Taiwan 2Austria*

**Quality of Life of Patients with Ovarian Cancer**

Ovarian cancer is one of the leading female cancers around the world (International Agency for Research on Cancer, 2011). Up to now, there is no effective method of early detection (US Task Force of Preventive Services, 2011). When detected, the stages are usually advanced, and patients have poor prognosis and poor health-related quality of life (HRQoL). Patientreported outcomes have been recommended as endpoints of clinical trials by the U.S. Food and Drug Administration (FDA) (2011). Therefore, besides improving survival, a better HRQoL is a major goal for the development of methods for new detection and treatments.

Patients with ovarian cancer share general functioning and systemic problems with patients with other cancers (Cella et al., 1993; Cain et al., 1998; Base-Enquist et al., 2001; Aaronson et al., 1993). Regarding disease-specific problems, abdominal / gastrointestinal symptoms because of the space-occupying nature of the tumor and the malignant ascites from the tumor in the pelvic and abdominal cavity are most important issues (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b). The disease recurs easily. Patients may

The standard treatment of this disease is debulking (cytoreduction) surgery followed by platinum-based chemotherapy (du Bois at al., 2005), while a new approach of neoadjuvant chemotherapy followed by debulking surgery (Brisow & Chi, 2006). These treatments, no matter which comes first, can improve survival and improve HRQoL of patients by reducing tumor size and ascites, and also patients' psychological distress. But they may also have negative impacts on HRQoL of patients because of the adverse effects of chemotherapy

The life-threatening nature of the illness can also cause psychological distress (Cull et al., 2001; Greimel et al., 2003a, 2003b). As all other gynecological cancers, patients with ovarian

suffer repeating debulking surgeries and chemotherapies that affect their HRQoL.

**1. Introduction**

**1.1 Current status of ovarian cancer**

**1.2 The impacts of the disease**

**1.3 The impacts of the treatments**

**1.4 Other important aspects of HRQoL**

and surgery.

*2Department of Obstetrics and Gynaecology, Medical University Graz, Graz*

Wei-Chu Chie1 and Elfriede Greimel2

*1Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University*

[48] Wright JD, Shah M, Mathew L, Burke WM, Culhane J, Goldman N, Schiff PB, Herzog TJ. Fertility preservation in young women with epithelial ovarian cancer. Cancer. 2009 Sep 15;115(18):4118-26.

## **Quality of Life of Patients with Ovarian Cancer**

### Wei-Chu Chie1 and Elfriede Greimel2

*1Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University 2Department of Obstetrics and Gynaecology, Medical University Graz, Graz 1Taiwan 2Austria*

### **1. Introduction**

326 Ovarian Cancer – Clinical and Therapeutic Perspectives

[48] Wright JD, Shah M, Mathew L, Burke WM, Culhane J, Goldman N, Schiff PB, Herzog

2009 Sep 15;115(18):4118-26.

TJ. Fertility preservation in young women with epithelial ovarian cancer. Cancer.

### **1.1 Current status of ovarian cancer**

Ovarian cancer is one of the leading female cancers around the world (International Agency for Research on Cancer, 2011). Up to now, there is no effective method of early detection (US Task Force of Preventive Services, 2011). When detected, the stages are usually advanced, and patients have poor prognosis and poor health-related quality of life (HRQoL). Patientreported outcomes have been recommended as endpoints of clinical trials by the U.S. Food and Drug Administration (FDA) (2011). Therefore, besides improving survival, a better HRQoL is a major goal for the development of methods for new detection and treatments.

### **1.2 The impacts of the disease**

Patients with ovarian cancer share general functioning and systemic problems with patients with other cancers (Cella et al., 1993; Cain et al., 1998; Base-Enquist et al., 2001; Aaronson et al., 1993). Regarding disease-specific problems, abdominal / gastrointestinal symptoms because of the space-occupying nature of the tumor and the malignant ascites from the tumor in the pelvic and abdominal cavity are most important issues (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b). The disease recurs easily. Patients may suffer repeating debulking surgeries and chemotherapies that affect their HRQoL.

### **1.3 The impacts of the treatments**

The standard treatment of this disease is debulking (cytoreduction) surgery followed by platinum-based chemotherapy (du Bois at al., 2005), while a new approach of neoadjuvant chemotherapy followed by debulking surgery (Brisow & Chi, 2006). These treatments, no matter which comes first, can improve survival and improve HRQoL of patients by reducing tumor size and ascites, and also patients' psychological distress. But they may also have negative impacts on HRQoL of patients because of the adverse effects of chemotherapy and surgery.

### **1.4 Other important aspects of HRQoL**

The life-threatening nature of the illness can also cause psychological distress (Cull et al., 2001; Greimel et al., 2003a, 2003b). As all other gynecological cancers, patients with ovarian

Quality of Life of Patients with Ovarian Cancer 329

problem, patients may have negative emotions (Cella et al., 1993; Aaronson et al., 1993), or suffer from burdens of and worries about disease or treatment (Cull et al., 2001; Greimel et

Like all other gynecological cancers, sexuality is negatively affected.  Dry vagina during intercourse, a result of hormonal depletion, can also be classified in this category (Cull et al., 2001; Greimel et al., 2003a,

We have at present two systems of disease-specific instruments for assessment of HRQoL of patients with ovarian cancer: the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer (EORTC). Both have a generic core questionnaire, the FACT-G and the EORTC QLQ-C30, and a disease-specific

The FACT-G was developed as a general measure for HRQoL of patients with cancer in 1987 (Cella et al., 1993) and validated in patients with different cancers before the development of ovarian specific scale (Weitzner et al., 1995; Cella, 1995; List at al., 1996; Brady at al., 1997; Esper at al., 1997; Yellen at al., 1997; McQuellon et al., 1997; Ward at al., 1999). The instrument contains four domains and 27 questions: physical well-being (PWB), 7 questions; social / family well-being (SWB), 7 questions; emotional well-being (EWB), 6 questions; and functional well-being (FWB), 7 questions (Cella et al., 1993). Each question has 5 options: 0 (not at all), 1 (a little bit), 3 (quite a bit), and 4 (very much). All item scores are recoded to make a high score corresponding to better HRQoL. It can be seen either as a disease-specific instrument vs. other diseases or a generic instrument for all patients with cancer. An ovarian cancer-specific subscale (OCS) was developed in 1998 using the same option format (Cain et al., 1998) and was reported to have good reliability and validity in 2001 (Base-Enquist et al., 2001). The questionnaire contains one domain, originally 12 questions: stomach swelling, losing weight, vomiting, hair loss, stomach cramping, and concerns about fertility (negative questions); bowel control, good appetite, appearance, getting around, feel like a woman, and interested in sex (positive questions, reverse coded). One question (concerns about fertility) was deleted because most patients are beyond childbearing age. The two instruments are used together when assessing HRQoL of patients with ovarian cancer. The score of each scale is a summation of recoded question scores within each scale. The total score is a

**3. Existing instruments for assessment of HRQoL**

**3.1 The FACT system: FACT-G and FACT-O 3.1.1 The scale structure of the FACT system**

supplementary questionnaire, the FACT-O and the EORTC QLQ-OV28.

summation of all scores of all 38 (27 and 11) questions together.

**3.1.2 Reliability and validity of the FACT system in patients with ovarian cancer**  Reliability and validity of the FACT-O with FACT-G were reported by Base-Enquist et al. (2001). The internal consistency (Cronbach's alpha) coefficient of the 11 questions in FACT-O was 0.92, and test-retest correlation coefficient of the total FACT-O score was 0.81.

### **2. Domains of HRQoL affected by disease and treatments of ovarian cancer**

### **2.1 Disease-related problems**

### **2.1.1 General functioning and systemic symptoms**

General functioning including physical, emotional, social, etc. (Cella et al., 1993; Aaronson et al., 1993) and ability of getting around (independence) are major issues in this category (Cain et al., 1998; Base-Enquist et al., 2001). Weight loss is also seen as a disease-related systemic symptom for advanced tumor (Cain et al., 1998; Base-Enquist et al., 2001).

### **2.1.2 Abdominal (gastrointestinal) symptoms**

Abdominal (gastrointestinal) symptoms are major disease-related HRQoL problems of patients with ovarian cancer. These symptoms may include abdominal swelling, fullness, pain or cramps, indigestion, change of bowel habit, etc. Abdominal pain and bowel habit change can also arise from treatment (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b).

### **2.2. Treatment-related problems**

### **2.2.1 Urological and gynecological symptoms**

The urological or gynecological symptoms are not as common as other gynecological cancers, and they are usually caused by treatment.  Urinary frequency can also be attributed to chemotherapy (Cull et al., 2001; Greimel et al., 2003a, 2003b).

### **2.2.3 Termination of reproductive ability and menopausal symptoms**

For women of reproductive age, both surgical treatment and chemotherapy can cause early menopause and the termination of reproductive ability (Cain et al., 1998; Base-Enquist et al., 2001). Menopausal symptoms caused by hormonal depletion, including hot flush (flash) and night sweats, are also experienced by these patients (Cull et al., 2001; Greimel et al., 2003a, 2003b).

### **2.3 Other important aspects in HRQoL**

### **2.3.1 Body image and psychological problems**

Like all other gynecological cancer, ovarian cancer per se and its treatment can cause body image and psychological problems. For the body image problems, patients may feel less attractive, less like a woman, dissatisfied with body or appearance, etc. (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b). For the psychological problem, patients may have negative emotions (Cella et al., 1993; Aaronson et al., 1993), or suffer from burdens of and worries about disease or treatment (Cull et al., 2001; Greimel et al., 2003a, 2003b).

### **2.3.2 Sexuality**

328 Ovarian Cancer – Clinical and Therapeutic Perspectives

cancer suffer from body image concerns and problems in sexual life (Cain et al., 1998; Base-

**2. Domains of HRQoL affected by disease and treatments of ovarian cancer**

General functioning including physical, emotional, social, etc. (Cella et al., 1993; Aaronson et al., 1993) and ability of getting around (independence) are major issues in this category (Cain et al., 1998; Base-Enquist et al., 2001). Weight loss is also seen as a disease-related

Abdominal (gastrointestinal) symptoms are major disease-related HRQoL problems of patients with ovarian cancer. These symptoms may include abdominal swelling, fullness, pain or cramps, indigestion, change of bowel habit, etc. Abdominal pain and bowel habit change can also arise from treatment (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al.,

The urological or gynecological symptoms are not as common as other gynecological cancers, and they are usually caused by treatment.  Urinary frequency can also be attributed to

For women of reproductive age, both surgical treatment and chemotherapy can cause early menopause and the termination of reproductive ability (Cain et al., 1998; Base-Enquist et al., 2001). Menopausal symptoms caused by hormonal depletion, including hot flush (flash) and night sweats, are also experienced by these patients (Cull et al., 2001; Greimel et al., 2003a,

Like all other gynecological cancer, ovarian cancer per se and its treatment can cause body image and psychological problems. For the body image problems, patients may feel less attractive, less like a woman, dissatisfied with body or appearance, etc. (Cain et al., 1998; Base-Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b). For the psychological

systemic symptom for advanced tumor (Cain et al., 1998; Base-Enquist et al., 2001).

Enquist et al., 2001; Cull et al., 2001; Greimel et al., 2003a, 2003b).

**2.1.1 General functioning and systemic symptoms**

**2.1.2 Abdominal (gastrointestinal) symptoms**

**2.2.1 Urological and gynecological symptoms**

often complained of (Cull et al., 2001; Greimel et al., 2003a, 2003b).

chemotherapy (Cull et al., 2001; Greimel et al., 2003a, 2003b).

**2.2.3 Termination of reproductive ability and menopausal symptoms**

**2.1 Disease-related problems**

2001; Greimel et al., 2003a, 2003b).

**2.2. Treatment-related problems**

**2.2.2 Chemotherapy side effects**

**2.3 Other important aspects in HRQoL**

**2.3.1 Body image and psychological problems**

2003b).

Like all other gynecological cancers, sexuality is negatively affected.  Dry vagina during intercourse, a result of hormonal depletion, can also be classified in this category (Cull et al., 2001; Greimel et al., 2003a, 2003b).

### **3. Existing instruments for assessment of HRQoL**

We have at present two systems of disease-specific instruments for assessment of HRQoL of patients with ovarian cancer: the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer (EORTC). Both have a generic core questionnaire, the FACT-G and the EORTC QLQ-C30, and a disease-specific supplementary questionnaire, the FACT-O and the EORTC QLQ-OV28.

### **3.1 The FACT system: FACT-G and FACT-O**

### **3.1.1 The scale structure of the FACT system**

The FACT-G was developed as a general measure for HRQoL of patients with cancer in 1987 (Cella et al., 1993) and validated in patients with different cancers before the development of ovarian specific scale (Weitzner et al., 1995; Cella, 1995; List at al., 1996; Brady at al., 1997; Esper at al., 1997; Yellen at al., 1997; McQuellon et al., 1997; Ward at al., 1999). The instrument contains four domains and 27 questions: physical well-being (PWB), 7 questions; social / family well-being (SWB), 7 questions; emotional well-being (EWB), 6 questions; and functional well-being (FWB), 7 questions (Cella et al., 1993). Each question has 5 options: 0 (not at all), 1 (a little bit), 3 (quite a bit), and 4 (very much). All item scores are recoded to make a high score corresponding to better HRQoL. It can be seen either as a disease-specific instrument vs. other diseases or a generic instrument for all patients with cancer. An ovarian cancer-specific subscale (OCS) was developed in 1998 using the same option format (Cain et al., 1998) and was reported to have good reliability and validity in 2001 (Base-Enquist et al., 2001). The questionnaire contains one domain, originally 12 questions: stomach swelling, losing weight, vomiting, hair loss, stomach cramping, and concerns about fertility (negative questions); bowel control, good appetite, appearance, getting around, feel like a woman, and interested in sex (positive questions, reverse coded). One question (concerns about fertility) was deleted because most patients are beyond childbearing age. The two instruments are used together when assessing HRQoL of patients with ovarian cancer. The score of each scale is a summation of recoded question scores within each scale. The total score is a summation of all scores of all 38 (27 and 11) questions together.

### **3.1.2 Reliability and validity of the FACT system in patients with ovarian cancer**

Reliability and validity of the FACT-O with FACT-G were reported by Base-Enquist et al. (2001). The internal consistency (Cronbach's alpha) coefficient of the 11 questions in FACT-O was 0.92, and test-retest correlation coefficient of the total FACT-O score was 0.81. The correlation coefficients between the total FACT-O score, subscale scores of FACT-G, and

Quality of Life of Patients with Ovarian Cancer 331

0.90). There was no scaling error except the subscale of other chemotherapy side effects (5/42). The intraclass correlation coefficients for test-retest of all subscales ranged from 0.74 to 0.94. The correlation coefficients between subscales of the EORTC QLQ-OV28 and EORTC QLQ-C30 were as expected. For responsiveness, scores of abdominal symptoms, peripheral neuropathy, other chemotherapy side effects, and disease burden responded significantly after treatment. For sensitivity (known-groups comparison), subscale scores differed most significantly between patients with primary and recurrent tumors. According to the validation report, the EORTC QLQ-OV28 is a reliable and valid multi-dimensional instrument used with the EORTC QLQ-C30 for the assessment of HRQoL of multiple

The comparison of the two sets of instruments is shown in Tables 1 and 2. The functional scales of the FACT-G and the EORTC QLQ-C30 are similar. Both include physical, mental or emotional, social, and role or functional subscales. The FACT-G emphasizes familial functioning, while the EORTC QLQ-C30 includes cognitive functioning. Both have an overall measure for HRQoL: the FACT-G uses a summation of all scores, while the EORTC QLQ-C30 measures it separately. The EORTC QLQ-C30 also has symptom and financial difficulty subscales. The FACT-G includes some symptoms in physical or function subscales (Table 1). The contents of the FACT-O and the EORTC QLQ-OV28 are similar. However, the FACT-O has only one overall scale for ovarian cancer, while the EORTC QLQ-OV28 has seven subscales covering problems of different organ-systems or

**Physical** Energy **Physical** Strenuous activity

Nausea Long walk Family needs Short walk Pain Stay in chair Side effects Self-care

**Social /family** Close to friends **Social** Interfere with family life

Satisfied with coping Worry Losing hope Irritable Feel nervous Depressed Worry / dying **Cognitive** Concentration Worry / getting worse Remembering

Family support With social activities

aspects for patients with ovarian cancer.

aspects of HRQoL (Table 2).

**3.3 Comparison of scale structures of the two systems**

**FACT EORTC**

Friends' support Family comm. illness Close to partner Sexual life

**Emotional** Feel sad **Emotional** Tense

Feel ill

Bed-ridden

subscale scores of other related instruments were as expected (good convergent and divergent validity). The scores of subscales of the FACT-G and the total FACT-O score were significantly different in different performance and treatment status, and were sensitive to changes of performance status. According to the validation results, the FACT-O is a reliable and valid instrument used with the FACT-G in assessment of ovarian cancer-specific HRQoL as a whole for patients with ovarian cancer.

### **3.2 The EORTC system: QLQ-C30 and QLQ-OV28 3.2.1 The scale structure of the EORTC system**

The development of the EORTC QLQ-C30 can be traced back in 1986. The questionnaire was designed for the measurement of general HRQoL issued for patients with cancer (Aaronson et al., 1993). It can also be seen either as a disease-specific instrument vs. other diseases or a generic instrument for all patients with cancer. The questionnaire contains 30 questions belonging to five functional scales (physical, role, emotional, social, and cognitive), nine symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, and diarrhea), financial difficulty in the past week, and one global health status (overall health and quality of life) scale. Each question has 4 options: 1 (not at all), 2 (a little), 3 (quite a bit), and 4 (very much). Each scale is scored separately. There is no total score. All scale scores are transformed into 0-100 from a recoded summation of item scores in each scale. For all functional scales, a higher score represents a better HRQoL. For all symptom scales and financial difficulty, a higher score means a poorer HRQoL. Previous studies showed good reliability and validity for different cancer diagnoses (Bjordal & Kaasa, 1992; Aaronson et al., 1993; Hjermstad et al., 1995; Groenvold et al., 1997; Kobayashi et al., 1998).

The EORTC QLQ-OV28 was designed as a supplement to the EORTC QLQ-C30 for the use in ovarian cancer clinical trials and related studies (Cull et al., 2001; Greimel et al., 2003a, 2003b). It contains seven subscales and 28 questions – abdominal / gastrointestinal symptoms (7 questions: abdominal pain, feeling bloated, clothes too tight, changed bowel habit, flatulence, fullness when eating, indigestion), peripheral neuropathy (4 questions: tingling, numbness, and weakness), other chemotherapy side-effects (7 questions: hair loss and upset by hair loss, taste change, muscle pain, hearing problem, urinary frequency, and skin problem), hormonal / menopausal (2 questions: hot flushes and night sweat), body image (2 questions: less attractive, dissatisfied with body), attitude to disease and treatment (3 questions: disease burden, treatment burden, and worry about future), and sexual function (4 questions: interest in sex, sexual activity, enjoyment of sex, and dry vagina). Each scale is scored separately as that of the EORTC QLQ-C30. For symptom scales, a higher score means a poorer HRQoL. For function scales (body image and sexual function), a higher score represent a better HRQoL. In addition to the cross-cultural validation of the EORTC, Chie et al. (2010) reported the translation and validation of the EORTC QLQ-OV28 in Taiwan and found a relatively low importance of body image, menopausal, and sexuality problems because of low emphasis on attractiveness and avoidance of sexual activity after having cancer.

### **3.2.2 Reliability and validity of the EORTC system in patients with ovarian cancer**

Greimel et al. (2003b) reported the result of cross-cultural validation of the EORTC QLQ-OV28 used with the EORTC QLQ-C30. The internal consistency (Cronbach's alpha) coefficients of all subscales except body image (0.58) were above 0.70 (ranging from 0.77 to

subscale scores of other related instruments were as expected (good convergent and divergent validity). The scores of subscales of the FACT-G and the total FACT-O score were significantly different in different performance and treatment status, and were sensitive to changes of performance status. According to the validation results, the FACT-O is a reliable and valid instrument used with the FACT-G in assessment of ovarian cancer-specific

The development of the EORTC QLQ-C30 can be traced back in 1986. The questionnaire was designed for the measurement of general HRQoL issued for patients with cancer (Aaronson et al., 1993). It can also be seen either as a disease-specific instrument vs. other diseases or a generic instrument for all patients with cancer. The questionnaire contains 30 questions belonging to five functional scales (physical, role, emotional, social, and cognitive), nine symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, and diarrhea), financial difficulty in the past week, and one global health status (overall health and quality of life) scale. Each question has 4 options: 1 (not at all), 2 (a little), 3 (quite a bit), and 4 (very much). Each scale is scored separately. There is no total score. All scale scores are transformed into 0-100 from a recoded summation of item scores in each scale. For all functional scales, a higher score represents a better HRQoL. For all symptom scales and financial difficulty, a higher score means a poorer HRQoL. Previous studies showed good reliability and validity for different cancer diagnoses (Bjordal & Kaasa, 1992; Aaronson et al., 1993; Hjermstad et al., 1995; Groenvold et al., 1997; Kobayashi et al.,

The EORTC QLQ-OV28 was designed as a supplement to the EORTC QLQ-C30 for the use in ovarian cancer clinical trials and related studies (Cull et al., 2001; Greimel et al., 2003a, 2003b). It contains seven subscales and 28 questions – abdominal / gastrointestinal symptoms (7 questions: abdominal pain, feeling bloated, clothes too tight, changed bowel habit, flatulence, fullness when eating, indigestion), peripheral neuropathy (4 questions: tingling, numbness, and weakness), other chemotherapy side-effects (7 questions: hair loss and upset by hair loss, taste change, muscle pain, hearing problem, urinary frequency, and skin problem), hormonal / menopausal (2 questions: hot flushes and night sweat), body image (2 questions: less attractive, dissatisfied with body), attitude to disease and treatment (3 questions: disease burden, treatment burden, and worry about future), and sexual function (4 questions: interest in sex, sexual activity, enjoyment of sex, and dry vagina). Each scale is scored separately as that of the EORTC QLQ-C30. For symptom scales, a higher score means a poorer HRQoL. For function scales (body image and sexual function), a higher score represent a better HRQoL. In addition to the cross-cultural validation of the EORTC, Chie et al. (2010) reported the translation and validation of the EORTC QLQ-OV28 in Taiwan and found a relatively low importance of body image, menopausal, and sexuality problems because of low emphasis on attractiveness and avoidance of sexual activity after

**3.2.2 Reliability and validity of the EORTC system in patients with ovarian cancer**  Greimel et al. (2003b) reported the result of cross-cultural validation of the EORTC QLQ-OV28 used with the EORTC QLQ-C30. The internal consistency (Cronbach's alpha) coefficients of all subscales except body image (0.58) were above 0.70 (ranging from 0.77 to

HRQoL as a whole for patients with ovarian cancer.

**3.2 The EORTC system: QLQ-C30 and QLQ-OV28 3.2.1 The scale structure of the EORTC system**

1998).

having cancer.

0.90). There was no scaling error except the subscale of other chemotherapy side effects (5/42). The intraclass correlation coefficients for test-retest of all subscales ranged from 0.74 to 0.94. The correlation coefficients between subscales of the EORTC QLQ-OV28 and EORTC QLQ-C30 were as expected. For responsiveness, scores of abdominal symptoms, peripheral neuropathy, other chemotherapy side effects, and disease burden responded significantly after treatment. For sensitivity (known-groups comparison), subscale scores differed most significantly between patients with primary and recurrent tumors. According to the validation report, the EORTC QLQ-OV28 is a reliable and valid multi-dimensional instrument used with the EORTC QLQ-C30 for the assessment of HRQoL of multiple aspects for patients with ovarian cancer.

### **3.3 Comparison of scale structures of the two systems**

The comparison of the two sets of instruments is shown in Tables 1 and 2. The functional scales of the FACT-G and the EORTC QLQ-C30 are similar. Both include physical, mental or emotional, social, and role or functional subscales. The FACT-G emphasizes familial functioning, while the EORTC QLQ-C30 includes cognitive functioning. Both have an overall measure for HRQoL: the FACT-G uses a summation of all scores, while the EORTC QLQ-C30 measures it separately. The EORTC QLQ-C30 also has symptom and financial difficulty subscales. The FACT-G includes some symptoms in physical or function subscales (Table 1). The contents of the FACT-O and the EORTC QLQ-OV28 are similar. However, the FACT-O has only one overall scale for ovarian cancer, while the EORTC QLQ-OV28 has seven subscales covering problems of different organ-systems or aspects of HRQoL (Table 2).

Quality of Life of Patients with Ovarian Cancer 333

Are the results of the two systems equivalent? Hozner et al. (2006) reported a study on 737 patients with different cancers for the equivalence of the FACT-G and the EORTC QLQ-C30, the core content of the two systems. Both classical test theory and Rasch measurement model were used. Three of the four subscales common to the two systems are equating: physical, emotional, and role / functional, but not the social / family subscale. A converting table was generated according to the results. No such study was conducted for the FACT-O and the EORTC QLQ-OV28 because the FACT-O has only one subscale, therefore the two

**5. Application of two systems in assessing HRQoL of patients with ovarian**

The two systems of instruments measuring HRQoL of patients with ovarian cancer were used in clinical trials and non-trial clinical studies. The FACT system was more widely used because the FACT-O was developed earlier than the EORTC QLQ-OV28. The FACT-O has been applied in studies assessing palliative chemotherapy for advanced ovarian cancer (using EORTC QLQ-C30 and FACT-O) (Doyle et al., 2001), general chemotherapy ( Le et al., 2004), adjuvant and salvage chemotherapy for advanced ovarian cancer (Le et al., 2005), interval cytoreduction in advanced ovarian cancer (Wenzel et al., 2005), active coping (Canada et al., 2006), Thallidomide therapy (Gordinier et al., 2007), phase I/II gemcitabine and doxirubicine (Goff et al., 2003)] and phase II gemicitabine and topotecan trials for platinum-refractory ovarian cancers (Goff et al., 2008), and factors for decreased QoL (von Gruenigen et al., 2009). In summary, the FACT-O and FACT-G scores became better when there was response to treatment, active coping can improve HRQoL, and factors causing

The use of the EORTC QLQ-OV28 with the EORTC QLQ-C30 was less common because it was developed later than the FACT-O. The two questionnaires were first used in a study assessing HRQoL for patients after pelvic exenteration in 2004 (Roos et al., 2004) where more physical, social, and sexual problems, especially for young patients were reported after surgery. A comparison of HRQoL of patients with early vs. advanced ovarian cancer (Mirabeau-Beale et al., 2009) found comparable HRQoL in two groups. A clinical trial of neoadjuvant platinum-based chemotherapy followed by (interval) debulking surgery vs. standard care of primary debulking surgery followed by platinum-based chemotherapy in stage IIIC or IV ovarian cancer used the two questionnaires did not detect any difference between the two arms in HRQoL (Vergote et al., 2010). The EORTC QLQ-C30 alone without the EORTC QLQ-OV28 has been used in a randomized trial of cisplatin / paclitaxel vs. carboplatin / paclitaxel and found patients undergoing carboplatin / paclitaxel treatment had better HRQoL (Greimel et al., 2006). Another study using the EORTC QLQ-C30 assessing the HRQoL of long-term survivors of ovarian cancer found long-term survivors had better HRQoL scores before treatment than short-term survivors, and long-term survivors had significant improvement of HRQoL in emotional and global health scores 1 year after treatment and remained stable. The scores of all domains but dyspnea were

**cancer undergoing different treatments across different cultures**

**4. Equivalence of the FACT and the EORTC systems**

site-specific questionnaires have no common subscales to study.

decreased HRQoL can be detected and managed in advance.

comparable with women without cancer (Greimel et al., 2011).

**5.2 The application of the EORTC system**

**5.1 The application of the FACT system**

Table 1. Comparison of FACT-G and the EORTC QLQ-C30.

Table 2. Comparison of FACT-O and the EORTC QLQ-OV28.

Content with QOL **Overall** Health

Work fulfilling Limited leisure

diarrhea

**Peripheral neuropathy**

**chemotherapy side effects**

**Attitude to disease**

**Other**

Dyspnea, Sleep, Appetite, constipation,

**GI symptoms** Abdominal pain,

Feeling bloated, Clothes tight, Changed bowel habit, Flatulence, Fullness when eating, Indigestion

Tingling, Numbness, Weakness

Hair loss & upset, Taste change, Muscle pain, Hearing problem, Urinary frequency, Skin problem

Disease burden, Treatment burden, Worry about future

Sexual activity, Sex enjoyment, Dry

vagina

**Sexual function** Interest in sex,

**Functional** Able to work **Role** Limited work

**Symptoms** Pain, Fatigue, Nausea & vomiting

QOL

**Other scale(s)** Financial difficulty

Table 1. Comparison of FACT-G and the EORTC QLQ-C30.

**FACT EORTC**

Table 2. Comparison of FACT-O and the EORTC QLQ-OV28.

Stomach swelling, losing weight, bowel control, vomiting, hair loss, good appetite, appearance, getting around, feel like a woman, stomach cramping, interested in sex,

concerns about fertility (deleted)

**FACT-O** (one scale)

**FACT EORTC**

Enjoy life Sleep well Enjoy pleasure

### **4. Equivalence of the FACT and the EORTC systems**

Are the results of the two systems equivalent? Hozner et al. (2006) reported a study on 737 patients with different cancers for the equivalence of the FACT-G and the EORTC QLQ-C30, the core content of the two systems. Both classical test theory and Rasch measurement model were used. Three of the four subscales common to the two systems are equating: physical, emotional, and role / functional, but not the social / family subscale. A converting table was generated according to the results. No such study was conducted for the FACT-O and the EORTC QLQ-OV28 because the FACT-O has only one subscale, therefore the two site-specific questionnaires have no common subscales to study.

### **5. Application of two systems in assessing HRQoL of patients with ovarian cancer undergoing different treatments across different cultures**

### **5.1 The application of the FACT system**

The two systems of instruments measuring HRQoL of patients with ovarian cancer were used in clinical trials and non-trial clinical studies. The FACT system was more widely used because the FACT-O was developed earlier than the EORTC QLQ-OV28. The FACT-O has been applied in studies assessing palliative chemotherapy for advanced ovarian cancer (using EORTC QLQ-C30 and FACT-O) (Doyle et al., 2001), general chemotherapy ( Le et al., 2004), adjuvant and salvage chemotherapy for advanced ovarian cancer (Le et al., 2005), interval cytoreduction in advanced ovarian cancer (Wenzel et al., 2005), active coping (Canada et al., 2006), Thallidomide therapy (Gordinier et al., 2007), phase I/II gemcitabine and doxirubicine (Goff et al., 2003)] and phase II gemicitabine and topotecan trials for platinum-refractory ovarian cancers (Goff et al., 2008), and factors for decreased QoL (von Gruenigen et al., 2009). In summary, the FACT-O and FACT-G scores became better when there was response to treatment, active coping can improve HRQoL, and factors causing decreased HRQoL can be detected and managed in advance.

### **5.2 The application of the EORTC system**

The use of the EORTC QLQ-OV28 with the EORTC QLQ-C30 was less common because it was developed later than the FACT-O. The two questionnaires were first used in a study assessing HRQoL for patients after pelvic exenteration in 2004 (Roos et al., 2004) where more physical, social, and sexual problems, especially for young patients were reported after surgery. A comparison of HRQoL of patients with early vs. advanced ovarian cancer (Mirabeau-Beale et al., 2009) found comparable HRQoL in two groups. A clinical trial of neoadjuvant platinum-based chemotherapy followed by (interval) debulking surgery vs. standard care of primary debulking surgery followed by platinum-based chemotherapy in stage IIIC or IV ovarian cancer used the two questionnaires did not detect any difference between the two arms in HRQoL (Vergote et al., 2010). The EORTC QLQ-C30 alone without the EORTC QLQ-OV28 has been used in a randomized trial of cisplatin / paclitaxel vs. carboplatin / paclitaxel and found patients undergoing carboplatin / paclitaxel treatment had better HRQoL (Greimel et al., 2006). Another study using the EORTC QLQ-C30 assessing the HRQoL of long-term survivors of ovarian cancer found long-term survivors had better HRQoL scores before treatment than short-term survivors, and long-term survivors had significant improvement of HRQoL in emotional and global health scores 1 year after treatment and remained stable. The scores of all domains but dyspnea were comparable with women without cancer (Greimel et al., 2011).

Quality of Life of Patients with Ovarian Cancer 335

Basen-Enquist K, Bodurka-Bevers D, Fitzderald MA, et al. (2001). Reliability and validity of

Bjordal K, Kaasa S. (1992). Psychometric validation of the EROTC Core Quality of Life

Brady MJ, Cella DF, Mo F, et al. (1997). Reliability and validity of the Functional Assessment

Brisow RE, Chi DS. (2006). Platinum-based neoadjuvant chemotherapy and interval surgical

Cain JM, Wenzel LB, Monk BJ, et al. (1998). Palliative care and quality of life considerations

Canada AL. Parker PA, de Moor JS, et al. (2006). Active coping mediates the association

Cella D, Tulsky DS, Gray G, et al. (1993). The Functional Assessment of Cancer Therapy

Cella DF. (1995). Reliability and validity of the Functional Assessment of Cancer Therapy-

Chie WC, Lan CY, Chiang C, Chen CA. (2010). Quality of life of patients with ovarian cancer

Cull A, Howat S, Greimel E, et al. (2001). Development of a European Organisation for

Doyle C, Crump M, Pintile M, Oza AM. (2001). Does palliative chemotherapy palliate?

du Bois A, Quinn M, Thigpen T, et al. (2005). 2004 Consensus Statements on the

Vol.15, No.3, (March 1997), pp.974-986, 1809-1817, ISSN 0732-183X.

Vol.103, No.3, (December 2006), pp.1070-1076, ISSN 0090-8258.

*Oncology* Vol.101, No.1 (April 2006), pp. 102-107, ISSN 0090-8258.

*Oncology* Vol.11, No.4, (April 1993), pp. 570-579, ISSN 0732-183X.

*Cancer* Vol.37, No.1, (January 2001), pp. 47-53, ISSN 0959-8049.

No.3, (March 1993), pp. 365-376, ISSN 0027-8874.

186X.

307, ISBN<PHONE_NUMBER>040.

pp.199-220, ISSN 0169-5002.

2001), pp. 1266-1274, ISSN 0732-183X.

ISSN 1099-1611.

0923-7534.

Vol.19, No.6, (March 2001), pp. 1809-1817, ISSN 0732-183X.

international clinical trials in oncology. *Journal of the National Cancer Institute* Vol.85,

the Functional Assessment of Cancer Therapy-Ovarian. *Journal of Clinical Oncology*

Questionnaire, 30-item version and a diagnosis-specific module for head and neck cancer patients. *Acta Oncologica* Vol.31, No.3, (March 1992), pp. 311-321, ISSN 0284-

of Cancer Therapy-Breast quality-of-life instrument. *Journal of Clinical Oncology*

cytoreduction for advanced ovarian cancer: a meta-analysis. *Gynecologic Oncology*

in the management of ovarian cancer. In: *Ovarian cancer-controversies in management*. Gershenson DM, McGuire WP (eds). New York, NY, Churchill Livingston, pp 281-

between religion / spirituality and quality of life in ovarian cancer. *Gynecologic*

Scale: development and validation of the general measure. *Journal of Clinical*

Lung (FACT-L) quality of life instrument. *Lung Cancer* Vol.12, No.3, (June 1995),

in taiwan: validation and application of the Taiwan Chinese version of the EORTC QLQ-OV28, brief report. *Psycho-Oncology* Vol.19, No.7, (July 2010), pp. 782-785,

Research and Treatment of Cancer questionnaire module to assess the quality of life of ovarian cancer patients in clinical trials: a progress report. *European Journal of*

Evaluation of expectation, outcomes, and cost in women receiving chemotherapy for advanced ovarian cancer. *Journal of Clinical Oncology* Vol.19, No.6, (February

management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian cancer Consensus conference (GCIC CCCC 2004). *Ann Oncol* Vol.16, No.suppl 8, (October 2005), pp.ivvv7-ivvv12, ISSN

### **5.3 A comparison of the two systems in HRQoL assessment**

A review article in 2010 commented after comparing all generic and specific questionnaires for HRQoL of patients with gynecologic cancers that there is little evidence that disease-, symptom- or treatment-specific instruments are more responsive or sensitive than generic or cancer-specific questionnaires, and a superior quality and quantity data reported for the FACT system compared with the EORTC system (Luckett et al., 2010). Nordin and Greimel on behalf of the EORTC Quality of Life Gynecology Group (2010) responded in a letter that such comments are not substantiated and provided examples of good results of crosscultural validation. In addition to the cross-cultural nature, the multi-dimensional structure of the EORTC system may also help clinical researchers and practitioners conduct more detailed assessment of different aspects of HRQoL of patients.

### **6. Future development**

Ovarian cancer is an important gynecological cancer which affects the survival and HRQoL of patients (International Agency for Research on Cancer, 2011). The keys to improve both survival and HRQoL are methods of early detection (US Task Force of Preventive Services, 2011) and effective treatment (du Bois at al., 2005; Brisow & Chi, 2006). We expect breakthroughs in both early detection and effective treatment in the near future. Patientreported outcomes have been recommended as endpoints of clinical trials by the U.S. Food and Drug Administration (FDA) (2011). To evaluate the effectiveness of these methods, HRQoL is an essential primary endpoint. Two systems of HRQoL assessment, i.e. the FACT and the EORTC systems are available. Both cover major issues of HRQoL and show good reliability and validity in previous reports and are used widely around the world in clinical trials and clinical studies. Therefore, we expect that the assessment of HRQoL of patients can be routinely included in clinical researches and practice, to understand and further improve patients' HRQoL.

### **7. Conclusions**

Ovarian cancer is one of the leading female cancers around the world. There is no effective method of early detection. When detected, the stages are usually advanced, and patients have poor health-related quality of life (HRQoL). The standard treatments of this disease including debulking surgery and chemotherapy can improve survival and may have either positive or negative impacts on HRQoL of patients. The disease recurs easily. Patients may suffer repeating debulking surgeries and chemotherapies that affect their HRQoL. In this chapter, we introduced and reviewed the scale structures, psychometric properties and clinical validities of existing instruments – the FACT system and the EORTC system for the assessment of HRQoL for patients with ovarian cancer, and report the results of their application in clinical trials and observational studies. We hope that HRQoL can be emphasized and routinely assessed for all patients with ovarian cancer in future clinical researches and practice.

### **8. References**

Aaronson NK, Ahmedzai A, Berman B, et al. (1993). The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in

A review article in 2010 commented after comparing all generic and specific questionnaires for HRQoL of patients with gynecologic cancers that there is little evidence that disease-, symptom- or treatment-specific instruments are more responsive or sensitive than generic or cancer-specific questionnaires, and a superior quality and quantity data reported for the FACT system compared with the EORTC system (Luckett et al., 2010). Nordin and Greimel on behalf of the EORTC Quality of Life Gynecology Group (2010) responded in a letter that such comments are not substantiated and provided examples of good results of crosscultural validation. In addition to the cross-cultural nature, the multi-dimensional structure of the EORTC system may also help clinical researchers and practitioners conduct more

Ovarian cancer is an important gynecological cancer which affects the survival and HRQoL of patients (International Agency for Research on Cancer, 2011). The keys to improve both survival and HRQoL are methods of early detection (US Task Force of Preventive Services, 2011) and effective treatment (du Bois at al., 2005; Brisow & Chi, 2006). We expect breakthroughs in both early detection and effective treatment in the near future. Patientreported outcomes have been recommended as endpoints of clinical trials by the U.S. Food and Drug Administration (FDA) (2011). To evaluate the effectiveness of these methods, HRQoL is an essential primary endpoint. Two systems of HRQoL assessment, i.e. the FACT and the EORTC systems are available. Both cover major issues of HRQoL and show good reliability and validity in previous reports and are used widely around the world in clinical trials and clinical studies. Therefore, we expect that the assessment of HRQoL of patients can be routinely included in clinical researches and practice, to understand and further

Ovarian cancer is one of the leading female cancers around the world. There is no effective method of early detection. When detected, the stages are usually advanced, and patients have poor health-related quality of life (HRQoL). The standard treatments of this disease including debulking surgery and chemotherapy can improve survival and may have either positive or negative impacts on HRQoL of patients. The disease recurs easily. Patients may suffer repeating debulking surgeries and chemotherapies that affect their HRQoL. In this chapter, we introduced and reviewed the scale structures, psychometric properties and clinical validities of existing instruments – the FACT system and the EORTC system for the assessment of HRQoL for patients with ovarian cancer, and report the results of their application in clinical trials and observational studies. We hope that HRQoL can be emphasized and routinely assessed for all patients with ovarian cancer in future clinical

Aaronson NK, Ahmedzai A, Berman B, et al. (1993). The European Organization for

Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in

**5.3 A comparison of the two systems in HRQoL assessment**

detailed assessment of different aspects of HRQoL of patients.

**6. Future development**

improve patients' HRQoL.

researches and practice.

**8. References**

**7. Conclusions**

international clinical trials in oncology. *Journal of the National Cancer Institute* Vol.85, No.3, (March 1993), pp. 365-376, ISSN 0027-8874.

Quality of Life of Patients with Ovarian Cancer 337

Kobayashi K, Takeda F, Teramukai S, et al. (1998). A cross-validation of the European

Le T, Leis A, Pahwa P, et al. (2004). Quality of life evaluation in patients with ovarian cancer

Le T, Hopkins L, Fung MFK. (2005). Quality of life assessment during adjuvant and salvage

List MA, D'Antionio LL, Cella DF, et al. (1996). The Performance Status Scale for head and

Neck Scale. *Cancer* Vol.77, No.11, (June 1996), pp.2294-2301, ISSN 1097-0142. Luckett T, King M, Butow P. et al. (2010). Assessing health-related quality of life in

*Gynecological Cancer* Vol.20, No.4, (May 2010), pp. 664-684, ISSN 1525-1438. McQuellon RP, Russell GB, Cella DF, et al. (1997). Quality of life measurement in bone

Mirabeau-Beale KL, Kornblith AB, Penson T, et al. (2009). Comparison of the quality of life

Nordin AJ, Greimel E on behalf of the EORTC Quality of Life Gynecology Group. (2010).

Roos EJ, de Graeff A, van Eijkeren MA, Boon TA, Heintz APM. (2004). Quality of life after

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/

Vergote I, Trope CG, Amant F, et al. (2010). Neoadjuvant chemotherapy or primary surgery

von Gruenigen VE, Huang HQ, Gil KM, et al. (2009). Assessment of factors that contribute to

*Cancer* Vol.115, No.20, (October 2009), pp. 4857-4864, ISSN 1097-0142. Ward WL, Hahn EA, Mo F, et al. (1999). Reliability and validity of the Functional

Vol.98, No.1, (July 2005), pp. 39-44, ISSN 0090-8258.

Vol.19, No.4, (February 1997), pp. 357-368, ISSN 0268-3369.

No.2, (August 2009), pp. 353-359, ISSN 0090-8258.

U.S. Food and Drug Administration. (July 2011). Available from

(September 2010), pp.943-953, ISSN 0028-4793.

The US Task force of preventive services. (July 2011). Available from

http://www.uspreventiveservicestaskforce.org/uspstf/uspsovar.htm

pp. 810-815, ISSN 0959-8049.

pp. 839-844 , ISSN 0090-8258.

1438.

9343.

ISSN 0090-8258.

Guidances/default.htm

Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer. *European Journal of Cancer* Vol.34, No.6, (May 1998),

during chemotherapy treatment. *Gynecologic Oncology* Vol.92, No.3, (March 2004),

chemotherapy for advance stage epithelial ovarian cancer. *Gynecologic Oncoogyl*

neck cancer patients and the Functional Assessment of Cancer Therapy –Head and

gynecologic oncology. A systematic review or questionnaires and their ability to detect clinically important difference and change. *International Journal of*

marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. *Bone Marrow Transplantation*

of early and advanced stage ovarian cancer survivors. *Gynecologic Oncology* Vol.114,

Assessing health-related quality of life in gynecologic oncology (letter). *International Journal of Gynecological Cancer* Vol.20, No.8, (November 2010), p. 1301, ISSN 1525-

pelvic extenteration. *Gynecologic Oncology* Vol.93, No.3, (June 2004), pp. 610-614,

in stage IIIc or IV ovarian cancer. *New England Journal of Medicine* Vol.363, No.10,

decreased quality of life in Gynecologic Oncology Group ovarian cancer trials.

Assessment of Cancer Therapy-Colorectal (FACT-C) Scale quality of life instrument. *Quality of Life Research* Vol. 8, No.3, (May 1999), pp.181-195, ISSN 0962-

Esper P, Mo F, Chodak G, et al. (1997). Measuring quality of life in men with prostate cancer

Goff BA, Thompson T, Greer BE, Jacobs A, Storer B. (2003). Treatment of recurrent

Goff BA, Holmberg LA, Veljovich D, Kurland BF. (2008). Treat of recurrent or persistent

Gordinier ME, Dizon DS, Weitzen S, et al. (2007). Oral thalidomide as palliative

Greimel ER, Bottomley A, Cull A, et al. (2003a). An international field study of the reliability

Greimel ER, Bottomley A, Cull A, et al. (2003b). Cooridgendum to "An international field

Greimel E, Bjelic-Radisic V, Pfisterer J. et al. (2006). Randomised study of the

Greimel E, Daghofer F Petru E. (2011). Prospective assessment of quality of life in long-term

Groenvold, M, Klee MC, Sprangers MAG, Aaronson NK. (1997). Validation of the EORTC

Hozner B, Bode RK, Hahn EA, et al. (2006). Equating EORTC QLQ-C30 and FACT-G scores

http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900#WOMEN

*Epidemiology* Vol.50, No.4, (April 1997), pp. 441-450, ISSN 0895-4356. Hjermstad MJ, Fossa SD, Bjordal K, Kaasa S. (1995). Test/retest study of the European

*Medicine* Vol.10, No.1, (February 2007), pp. 61-65, ISSN 1096-6218.

*Cancer* Vol.39, No.10, (July 2003), pp.1402-1408, ISSN 0959-8049.

No.17, (November 2003), pp. 2570, ISSN 0959-8049.

(December 2006), pp. 3169-3177, ISSN 0959-8049. International Agency for Research on Cancer. (2011). Available from

pp. 3005-3011, ISSN 1097-0215.

ISSN 0732-183X.

Vol.24, No.4, (February 2006), pp.579-585, ISSN 0732-183X.

Vol.50, No.6, (December 1997), pp. 920-928. ISSN 0090-4295.

0090-8258.

using the Functional Assessment of Cancer Therapy-Prostate instrument. *Urology*

platinum-resistent ovarian or peritoneal cancer with gemcitabine and doxorubicin. A phase I/II trial of the the Puget Sound Oncology Consortium. *American Journal of Obstetrics and Gynecology* Vol.188, No.6. (June 2003), pp. 1556-1564, ISSN 0002-9378.

platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer with gemcitabine and topotecan. A phase II trial of the Puget Sound Oncology Consortium. *Gynecologic Oncology* Vol.110, No.2, (August 2008), pp. 146-151, ISSN

chemotherapy in women with advanced ovarian cancer. *Journal of Palliative*

and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer. *European Journal of*

study of the reliability and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer": [European Journal of Cancer 39: 1402-1408.]. *European Journal of Cancer* Vol.39,

Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group comparing quality of life in patients with ovarian cancer treated with cisplatin/paclitaxel versus carboplatin/paclitaxel. *Journal of Clinical Oncology*

ovarian cancer survivors. *International Journal of Cancer* Vol.128, No.12 (June 2011),

QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement. *Journal of Clinical*

Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. *Journal of Clinical Oncology* Vol.13, No.5, (May 1995), pp. 1249-1254,

and its use in oncological research. *European Journal of Cancer* Vol.42, No.18,

Weitzner MA, Meyers CA, Gelke CK, et al. (1995). The Functional Assessment of Cancer

Wenzel L, Huang HQ, Monk BJ, Rrose PG, Cella D. (2005). Quality of life comparison in a

*Oncology* Vol.23, No.24, (August 2005), pp. 5605-5612, ISSN 0732-183X. Yellen SB, Cella DF, Webster K, et al. (1997). Measuring fatigue and other anemia-related

No.5, (March 1995), pp. 1151-1161, ISSN 1097-0142.

(February 1997), pp. 63-74, ISSN 0885-3924.

Therapy (FACT) Scale: development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. *Cancer* Vol.75,

randomized controlled trial of interval secondary cytoreduction in advanced ovarian carcinoma: a Gynecologic Oncology Group study. *Journal of Clinical*

symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. *Journal of Pain and Symptom Management* Vol.13, No.2

### *Edited by Samir A. Farghaly*

Worldwide, Ovarian carcinoma continues to be responsible for more deaths than all other gynecologic malignancies combined. International leaders in the field address the critical biologic and basic science issues relevant to the disease. The book details the molecular biological aspects of ovarian cancer. It provides molecular biology techniques of understanding this cancer. The techniques are designed to determine tumor genetics, expression, and protein function, and to elucidate the genetic mechanisms by which gene and immunotherapies may be perfected. It provides an analysis of current research into aspects of malignant transformation, growth control, and metastasis. A comprehensive spectrum of topics is covered providing up to date information on scientific discoveries and management considerations.

Ovarian Cancer - Clinical and Therapeutic Perspectives

Ovarian Cancer

Clinical and Therapeutic Perspectives

*Edited by Samir A. Farghaly*

Photo by xrender / iStock