*2.3.2 Maintenance and availability relationship*

The maintenance ability of system measures the effectiveness of a system in terms of ease and speed when the system and equipment return after failure. The possibility of a broken system can be restored to a definite period in operational conditions. Maintenance of availability becomes meaningful:

This makes the system inaccessible in operational areas (not operational). Accessibility does not mean that only the existing elements should be in operation but that backup systems require that, although we have a definite unit. The availability of a system can be related to the reliability of the system and the ease of repairing the system and sufficient reservoirs for spare parts. For mathematical analysis, we assume that there is a system that requires continuous operation, except in cases where we need preventive and planned maintenance. In this case, we estimate the temporary backup system, or the system will be definite for a

**101**

*ANFIS to Quantify Maintenance Cost of IT Services in Telecommunication Company*

short time, but it may be operational at this time, even though some of its elements are not available. This kind of failure can be tolerated until further preventive

The ultimate goal of a system's operation is that it is available when the system is needed. In systems, things such as failure rate, average repair time, one-piece delivery time, and operational constraints are all influence in accessibility. In the context of system maintenance analysis, review and measure the operating system and backup needs in quantitative and qualitative terms regarding design criteria in

In order to a system to be available, system providers should provide the required support over the life of the software and product. The ability to support the system requires an effective combination of reliability and maintenance and

Measuring the desirable performance and operational requirements of a computer system depends on our requests from the system. Performance measurement

When a computer system typically employs several types of activity, measuring the first feature is best done separately for any type of workload. Possible classifications for workload include timed checking, transaction processing, interactive computing, and categories. Errors create a variety of failures for the system, so all measurements in the category and the second floor must be evaluated for each type of error. For example, we should only use two types of error

Failure is visible effect of error. A catastrophic failure involves losing a significant amount of information, for example, a well-designed system. The CPU error

System performance is measured by the following assessment factors [9]:

1.**Responsiveness:** This measure evaluates how a task is executed rapidly by the system. Possible measurements include waiting time, processing time, conditional wait time (the wait time for an activity requires a certain amount

2.**Level of use:** This measure evaluates how a system uses its elements and components well. Possible measurements include operating power and the use of

2.How does a system deal with unusual failure and conditions?

3.How does the system use the available resources?

may be benign, but the disk error may be catastrophic.

of processing time), queue length, and so on

*2.4.1 Measuring system performance*

*DOI: http://dx.doi.org/10.5772/intechopen.82827*

hardware and backup requirements [8].

logistics and operational engineering.

**2.4 Metric software measurement**

depends on three factors [9]

1.Slow activity

classes:

• Catastrophic

• Benign

maintenance.

*ANFIS to Quantify Maintenance Cost of IT Services in Telecommunication Company DOI: http://dx.doi.org/10.5772/intechopen.82827*

short time, but it may be operational at this time, even though some of its elements are not available. This kind of failure can be tolerated until further preventive maintenance.

The ultimate goal of a system's operation is that it is available when the system is needed. In systems, things such as failure rate, average repair time, one-piece delivery time, and operational constraints are all influence in accessibility. In the context of system maintenance analysis, review and measure the operating system and backup needs in quantitative and qualitative terms regarding design criteria in hardware and backup requirements [8].

In order to a system to be available, system providers should provide the required support over the life of the software and product. The ability to support the system requires an effective combination of reliability and maintenance and logistics and operational engineering.

## **2.4 Metric software measurement**

Measuring the desirable performance and operational requirements of a computer system depends on our requests from the system. Performance measurement depends on three factors [9]

1.Slow activity

*Maintenance Management*

tester a software control.

*2.3.1 Maintenance activity*

into three phases:

3.Troubleshooting failure

4.Provided with spare parts

then we can measure its availability.

should be repaired or replaced.

lived as well as preventive maintenance operations.

conditions. Maintenance of availability becomes meaningful:

*2.3.2 Maintenance and availability relationship*

the problem in the least amount of time.

• If repairs need more time to fix.

• If installing spare parts is very hard.

• If spare parts are not available if they are needed.

• If the testing and alignment of spare parts are difficult.

Maintenance activity is limited to determining the defective unit and its replacement or a spare part. Defective units are repaired at a central location equipped with

Lalli et al. [8] said that maintenance is divided into two parts, which include the replacement of defective elements. Moreover, preventive maintenance, which includes scheduled maintenance in the design phase, separates maintenance activity

**In Phase I:** This includes planning and designing maintenance capability, which is part of a design process that involves the construction of elements that are easy to maintain and repair. In analyzing the measuring capability, the number of errors is often used from predictable times to maintain N's maintenance. Secondly, the expected time to maintain n is the expected maintenance with the program, as well as the expected time to repair and replace items that have a limited life span and a scheduled change program. Suppose the system is shut down during maintenance,

**In Phase II:** This includes handling failure and replacing items that are short-

**In Phase III:** This involves handling fault elements that specify whether it

The maintenance ability of system measures the effectiveness of a system in terms of ease and speed when the system and equipment return after failure. The possibility of a broken system can be restored to a definite period in operational

• If the system is interrupted and cannot be fixed in a minor way, we need to find

This makes the system inaccessible in operational areas (not operational). Accessibility does not mean that only the existing elements should be in operation but that backup systems require that, although we have a definite unit. The availability of a system can be related to the reliability of the system and the ease of repairing the system and sufficient reservoirs for spare parts. For mathematical analysis, we assume that there is a system that requires continuous operation, except in cases where we need preventive and planned maintenance. In this case, we estimate the temporary backup system, or the system will be definite for a

**100**

When a computer system typically employs several types of activity, measuring the first feature is best done separately for any type of workload. Possible classifications for workload include timed checking, transaction processing, interactive computing, and categories. Errors create a variety of failures for the system, so all measurements in the category and the second floor must be evaluated for each type of error. For example, we should only use two types of error classes:

Failure is visible effect of error. A catastrophic failure involves losing a significant amount of information, for example, a well-designed system. The CPU error may be benign, but the disk error may be catastrophic.

#### *2.4.1 Measuring system performance*

System performance is measured by the following assessment factors [9]:

different resources. The purpose of this measure is to measure responsiveness and differentiation and differences. Since a system that is well used is generally slower than the responsiveness system is less used.


**6. Management**

*Thymus*

**Table 2.**

*Masaoka-Koga staging system.*

Primary tumor (T)

Regional lymph nodes (N)

Distant metastases (M)

Prognostic stage groups

*TNM staging AJCC eighth edition.*

**TNM staging AJCC eighth edition**

**Masaoka-Koga stage** **Diagnostic criteria**

Stage IV a. Pleural or pericardial dissemination

TX Primary tumor cannot be assessed T0 No evidence of primary tumor

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases

N1 Metastases in anterior (perithymic) lymph nodes N2 Metastases in deep intrathoracic or cervical lymph nodes

M0 No pleural, pericardial, or distant metastases M1 Pleural, pericardial, or distant metastases

Stage I T1a,b N0 M0 Stage II T2 N0 M0 Stage IIIa T3 N0 M0 Stage IIIb T4 N0 M0

Stage IVa Any T N1

Stage IVb Any T N2

M1a separate pleural or pericardial nodules

T N M

N0–N1

Any N

M1b pulmonary intraparenchymal nodule or distant organ metastases

M0 M1a

M0–M1a M1b

encapsulated Stage II a. Microscopic transcapsular invasion

Stage I Macroscopically and microscopically completely

mediastinal pleura or pericardium

a. Without invasion in the great vessels b. With invasion in great vessels

b. Lymphogenous or hematogenous metastases

Stage III Macroscopic invasion into neighboring organs (i.e., pericardium, great vessels, lung)

T1 Tumor encapsulated or extending into the mediastinal fat may involve the mediastinal pleura T1a Tumor with no mediastinal pleural involvement T1b tumor with direct invasion of mediastinal pleura T2 Tumor with direct invasion of the pericardium (either partial or full thickness)

T3 Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior

T4 Tumor with invasion into any of the following: aorta, arch vessels, intrapericardial pulmonary artery, myocardium, or trachea esophagus

vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins

b. Macroscopic invasion into surrounding fatty tissue or grossly adherent to but not through

**80**

**Table 3.**

There are no phase III randomized, clinical trials on the treatment of thymoma and thymic carcinoma. Although they are two different entities, the general management per stage is almost the same. Surgery aimed at complete resection is the cornerstone of thymoma and thymic carcinoma management and should always be pursued.

All patients should be managed by a multidisciplinary team with experience in the management of thymoma and thymic carcinoma. The choice of treatment depends on resectability, stage, and whether or not myasthenia gravis is present. In all stages of thymoma and thymic carcinoma, resectability should be considered. When deemed possible in stages IIIb and IVa, surgery is part of a multimodality approach [25, 34–37].

An example of management according to stage could be as shown in **Table 4**. One should realize though that there is no advise based on phase III randomized controlled trails available and every case should be considered individually and there are different options, as discussed below.

## **6.1 Treatment thymoma**

## *6.1.1 Resectable disease*

Once complete resection of a thymoma is deemed possible, complete resection of the thymus, the tumor, and the invaded structures (including resection of the lung parenchyma or pericardium and vena cava reconstruction if necessary) is

#### **Table 4.**

*Treatment thymoma and thymic carcinoma according to stage.*

recommended [21, 25, 34, 36]. Preoperative evaluation for myasthenia gravis is advised. If this is diagnosed, treatment is essential, as myasthenia gravis can cause a postoperative myasthenic crisis or respiratory failure [38]. Thymoma Masaoka-Koga stages I and II have a 5-year survival rate of 100% after surgery [1].

In the case of an incomplete resection, postoperative radiotherapy (PORT), either on the primary tumor or on isolated metastasis, is recommended to reduce the risk of recurrence [35, 39]. In the past PORT was considered standard treatment for stage II completely resected tumors [7, 40]. Nowadays PORT in completely resected stages I and II WHO type A, AB, and B1 thymoma is not considered useful [10, 41–43]. Because of a high recurrence rate (even after R0 resection) PORT is advised for the higher stages and for WHO-type B2/3 thymoma and thymic carcinoma [21, 44], although the data are somewhat conflicting in this [7].

### *6.1.2 Potentially resectable disease*

More extensive thymomas can be initially irresectable but potentially resectable after neoadjuvant treatment. A multimodality approach containing neoadjuvant chemotherapy with or without postoperative radiotherapy should be used, depending on WHO type and resection margins [21, 35, 45–47].

Potential advantages of neoadjuvant chemotherapy are tumor downstaging and increasing the likelihood of complete resection. However, because the available data on chemotherapy in thymoma is based on small, phase II studies, there is no optimal chemotherapeutic regime established [21]. Potential disadvantages could be complications due to chemotherapy and longer operating time [48]. There is even some recent data suggesting that there is no overall survival benefit to be expected from neoadjuvant chemotherapy before surgery [48–50]. In the cases of extensive pleural disease, several institutions have reported small series of extrapleural pneumonectomy for stage IVA disease with excellent outcomes and low morbidity [51].

There are no RCT's available to settle this matter. For now, it is recommended to use neoadjuvant chemotherapy to downstage unresectable thymic malignancies before surgery [21]. Obviously, reevaluation after neoadjuvant therapy to determine whether or not the tumor responded sufficiently is mandatory. There is evidence supporting maximum debulking, combined with PORT and/or adjuvant chemotherapy, to benefit survival from a thymoma which turns out to be unresectable during surgery. This is, however, based on retrospective data, so selection bias could cloud this positive outcome [3, 52].

#### *6.1.3 Unresectable disease*

In the case of unresectable disease or the patients is inoperable due to condition or comorbidity, the possibility of radiation therapy should be assessed. If radiation is feasible, concurrent chemoradiation is advised. If radiation is not possible due to a too large field, palliative chemotherapy is recommended. But even in that setting, longterm disease control and survival can be sometimes pursued, and even a combination of radiation on the primary tumor combined with resection of metastasis could be considered [21].

**Chemotherapy** is the primary modality in systemic management of unresectable thymoma. Thymomas are known to be sensitive to chemotherapy, possible due to a "lymphocytic effect" of cytotoxic agents. Due to the rarity of the disease and surgery with or without PORT being the cornerstone of treatment, there are no randomized controlled trails available to select a preferred regime. Platinumbased combinations are standard of care, the most popular regimes being cisplatin with anthracycline and/or etoposide. The response rate range of these regimens is

**83**

*Thymoma and Thymic Carcinoma*

bicin/cyclophosphamide [21, 54].

opinion [21, 56, 57].

phase II data is available [60].

have a positive octreotide scan [64].

**6.2 Treatment thymic carcinoma**

*6.1.4 Recurrent disease*

safe [50, 65].

*DOI: http://dx.doi.org/10.5772/intechopen.87132*

between 25 and 100% [53]. The preferred regime by the NCCN is cisplatin/doxoru-

sis; conventional fractionation is appropriate for larger metastasis [21].

Stereotactic radiotherapy (SBRT) may be appropriate for limited focal metasta-

Response rates for second-line therapy range from 15 to 39% [55]. Pemetrexed and paclitaxel are considered the most efficacious in second-line treatment of thymic malignancies, although this is based on small phase II studies and expert

**Checkpoint inhibitors**. Programmed death ligand 1 (PD-L1) expression is high (82%) in thymoma, especially in WHO type B thymoma [58]. Even so, based on a phase II study on pembrolizumab (a humanized IgG4 antibody to PD-L1) in 33 thymic epithelial tumors (including 7 thymomas), immunotherapy is not recommended in thymoma. This is because of the high grade of immune-related events that was shown in seven thymoma patients during this study; 71% had grade 3 or higher immune-related adverse events (including myocarditis) [59]. Avelumab is a fully human IgG1 anti-PD-L1 antibody that showed less adverse events (38%) in a phase I trial (n = 7). However, it is currently under clinical development, and no

The high rate of immune-related side effect was expected; the physiological role of the thymus is to induce tolerance to self-antigens and deletion of autoimmune T cells. In the normal thymus, PD-1/PL-D1 expression regulates this self-tolerant T-cell repertoire. It is thought that disruption of the PD-1/PDL-1 system could lead to significant alteration of the T-cell population and therefore cause autoimmune-

**Targeted therapies**. Although there is high epidermal growth factor receptor (EGFR) expression in immunohistochemical staining of thymic epithelial tumors (71% for thymoma and 53% for thymic carcinoma), there is no correlation between the EGFR status and EGFR mutations. Experience with targeted therapies in thymoma is very limited and based on a small number of heterogenic phase II studies, but as for now this shows that there is no place for EGFR inhibitors in the treatment of thymoma and thymic carcinoma [7]. KIT-inhibition (inhibition of a transmembrane type III tyrosine kinase receptor) may show some promises in thymic carcinomas, but as thymomas do not show c-KIT expression [62], KIT-inhibition is not effective. There is some phase II experience in insulin-like growth factor (IGFR) inhibitors in thymoma patients that have shown some promising results [63]. Octreotide (a somatostatin analog) plus prednisolone may be useful in patients who

The recurrence rate of thymoma after complete resection is 10–30%, and this can occur many years after initial treatment. Surgical resection of recurrent disease can be associated with long-term survival and should be considered for patients with recurrent thymoma. In pleural "drop" lesions, repeated resection is considered

Similar to thymoma, surgery aimed at complete resection is the cornerstone of thymic carcinoma treatment, and the principles of first-line treatment in resectable disease are more or less the same. Five-year survival rate of 100% is reported for completely resected stage I disease going down to 17% in stage IVb disease [66]. Patients with a thymic carcinoma have a high risk of recurrent disease. Therefore,

related adverse events in the case of checkpoint inhibition [61].

#### *Thymoma and Thymic Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.87132*

*Thymus*

recommended [21, 25, 34, 36]. Preoperative evaluation for myasthenia gravis is advised. If this is diagnosed, treatment is essential, as myasthenia gravis can cause a postoperative myasthenic crisis or respiratory failure [38]. Thymoma Masaoka-

In the case of an incomplete resection, postoperative radiotherapy (PORT), either on the primary tumor or on isolated metastasis, is recommended to reduce the risk of recurrence [35, 39]. In the past PORT was considered standard treatment for stage II completely resected tumors [7, 40]. Nowadays PORT in completely resected stages I and II WHO type A, AB, and B1 thymoma is not considered useful [10, 41–43]. Because of a high recurrence rate (even after R0 resection) PORT is advised for the higher stages and for WHO-type B2/3 thymoma and thymic carci-

More extensive thymomas can be initially irresectable but potentially resectable after neoadjuvant treatment. A multimodality approach containing neoadjuvant chemotherapy with or without postoperative radiotherapy should be used, depend-

Potential advantages of neoadjuvant chemotherapy are tumor downstaging and increasing the likelihood of complete resection. However, because the available data on chemotherapy in thymoma is based on small, phase II studies, there is no optimal chemotherapeutic regime established [21]. Potential disadvantages could be complications due to chemotherapy and longer operating time [48]. There is even some recent data suggesting that there is no overall survival benefit to be expected from neoadjuvant chemotherapy before surgery [48–50]. In the cases of extensive pleural disease, several institutions have reported small series of extrapleural pneumonectomy for stage IVA disease with excellent outcomes and low morbidity [51]. There are no RCT's available to settle this matter. For now, it is recommended to use neoadjuvant chemotherapy to downstage unresectable thymic malignancies before surgery [21]. Obviously, reevaluation after neoadjuvant therapy to determine whether or not the tumor responded sufficiently is mandatory. There is evidence supporting maximum debulking, combined with PORT and/or adjuvant chemotherapy, to benefit survival from a thymoma which turns out to be unresectable during surgery. This is, however, based on retrospective data, so selection bias could

In the case of unresectable disease or the patients is inoperable due to condition or comorbidity, the possibility of radiation therapy should be assessed. If radiation is feasible, concurrent chemoradiation is advised. If radiation is not possible due to a too large field, palliative chemotherapy is recommended. But even in that setting, longterm disease control and survival can be sometimes pursued, and even a combination of radiation on the primary tumor combined with resection of metastasis could be

**Chemotherapy** is the primary modality in systemic management of unresectable thymoma. Thymomas are known to be sensitive to chemotherapy, possible due to a "lymphocytic effect" of cytotoxic agents. Due to the rarity of the disease and surgery with or without PORT being the cornerstone of treatment, there are no randomized controlled trails available to select a preferred regime. Platinumbased combinations are standard of care, the most popular regimes being cisplatin with anthracycline and/or etoposide. The response rate range of these regimens is

Koga stages I and II have a 5-year survival rate of 100% after surgery [1].

noma [21, 44], although the data are somewhat conflicting in this [7].

ing on WHO type and resection margins [21, 35, 45–47].

*6.1.2 Potentially resectable disease*

cloud this positive outcome [3, 52].

*6.1.3 Unresectable disease*

considered [21].

**82**

between 25 and 100% [53]. The preferred regime by the NCCN is cisplatin/doxorubicin/cyclophosphamide [21, 54].

Stereotactic radiotherapy (SBRT) may be appropriate for limited focal metastasis; conventional fractionation is appropriate for larger metastasis [21].

Response rates for second-line therapy range from 15 to 39% [55]. Pemetrexed and paclitaxel are considered the most efficacious in second-line treatment of thymic malignancies, although this is based on small phase II studies and expert opinion [21, 56, 57].

**Checkpoint inhibitors**. Programmed death ligand 1 (PD-L1) expression is high (82%) in thymoma, especially in WHO type B thymoma [58]. Even so, based on a phase II study on pembrolizumab (a humanized IgG4 antibody to PD-L1) in 33 thymic epithelial tumors (including 7 thymomas), immunotherapy is not recommended in thymoma. This is because of the high grade of immune-related events that was shown in seven thymoma patients during this study; 71% had grade 3 or higher immune-related adverse events (including myocarditis) [59]. Avelumab is a fully human IgG1 anti-PD-L1 antibody that showed less adverse events (38%) in a phase I trial (n = 7). However, it is currently under clinical development, and no phase II data is available [60].

The high rate of immune-related side effect was expected; the physiological role of the thymus is to induce tolerance to self-antigens and deletion of autoimmune T cells. In the normal thymus, PD-1/PL-D1 expression regulates this self-tolerant T-cell repertoire. It is thought that disruption of the PD-1/PDL-1 system could lead to significant alteration of the T-cell population and therefore cause autoimmunerelated adverse events in the case of checkpoint inhibition [61].

**Targeted therapies**. Although there is high epidermal growth factor receptor (EGFR) expression in immunohistochemical staining of thymic epithelial tumors (71% for thymoma and 53% for thymic carcinoma), there is no correlation between the EGFR status and EGFR mutations. Experience with targeted therapies in thymoma is very limited and based on a small number of heterogenic phase II studies, but as for now this shows that there is no place for EGFR inhibitors in the treatment of thymoma and thymic carcinoma [7]. KIT-inhibition (inhibition of a transmembrane type III tyrosine kinase receptor) may show some promises in thymic carcinomas, but as thymomas do not show c-KIT expression [62], KIT-inhibition is not effective. There is some phase II experience in insulin-like growth factor (IGFR) inhibitors in thymoma patients that have shown some promising results [63]. Octreotide (a somatostatin analog) plus prednisolone may be useful in patients who have a positive octreotide scan [64].

#### *6.1.4 Recurrent disease*

The recurrence rate of thymoma after complete resection is 10–30%, and this can occur many years after initial treatment. Surgical resection of recurrent disease can be associated with long-term survival and should be considered for patients with recurrent thymoma. In pleural "drop" lesions, repeated resection is considered safe [50, 65].

#### **6.2 Treatment thymic carcinoma**

Similar to thymoma, surgery aimed at complete resection is the cornerstone of thymic carcinoma treatment, and the principles of first-line treatment in resectable disease are more or less the same. Five-year survival rate of 100% is reported for completely resected stage I disease going down to 17% in stage IVb disease [66]. Patients with a thymic carcinoma have a high risk of recurrent disease. Therefore,

some centers offer PORT (with or without chemotherapy) regardless of stage and resection margins [3, 21]. The available data is yet again limited, and there are indications that adjuvant therapy is not beneficial in R0-resected stage I thymic carcinoma [21, 42, 67].

**Chemotherapy**. Thymic carcinomas respond less to chemotherapy than thymomas. Carboplatin/paclitaxel has the highest response rate in patients with thymic carcinoma, but even so this is only 22–36% [21, 55]. Response rates for second-line chemotherapy in thymic carcinoma are even worse (4–12%) [55].

**Checkpoint inhibitors**. Second-line treatment with pembrolizumab showed promising results in a phase II trial containing 40 patients with thymic carcinoma. There was an ORR of 22.5%, and the median duration of response was 22 months. While less in thymomas, there was still a high rate of immune-related adverse events (15%), including two cases of severe myocarditis [59]. A recently published study on nivolumab in thymic carcinoma patients showed no objective response in 15 patients, although 5 patients showed stable disease for more than 24 weeks [68].

**Targeted therapies**. The same as in thymoma, experience with targeted therapies in thymoma is very limited and based on small phase II studies and individual case reports. Sunitinib may be beneficial for patients with a c-KIT mutation, although the mutation rate is rare <10% [10, 69]. IGFR inhibition and octreotide did not show any activity in thymic carcinoma, in contrast to thymomas [63, 64].

#### **6.3 Follow-up**

After primary resection, expert opinion on follow-up consists of a CT scan every 6 months for 2 years, then annually for 5 years for thymic carcinoma and annually for 10 years for thymomas [21], although an exceptional case of late recurrence has been reported [70].

### **7. Conclusion**

Thymomas and thymic carcinomas are rare mediastinal tumors, and although the course of a thymoma can be indolent, they can indeed be locally invasive and metastasize. Thymic carcinomas more often are disseminated at presentation. Therefore, both are considered malignant. Forty to fifty percent of thymomas are related to autoimmune paraneoplastic syndromes, the most common being myasthenia gravis. Resection of the thymus can also act as treatment for the paraneoplastic syndrome. However, thymic treatment does not always resolve those paraneoplastic syndromes.

Because of the improved representation of the N-stage and correlation to prognosis, rather than surgical resectability, we recommend the AJCC eighth TMN classification.

There is no phase III data available on the management of thymic epithelial tumors. Surgery is considered the cornerstone of thymoma and thymic carcinoma management in resectable disease and even in recurrent disease. Neoadjuvant treatment and PORT should be considered according to stage.

In metastatic disease chemotherapy containing an anthracycline is advised. For recurrent metastatic disease sunitinib and octreotide, among other things, could be considered. A special note on checkpoint inhibitors should be made. Although they do show promising results in thymic carcinoma, the rate of immune-related adverse events is too high to consider this a valuable option for the treatment of thymoma right now.

**85**

**Author details**

Annette Rebecca Bijsmans and Robin Cornelissen\*

provided the original work is properly cited.

Erasmus MC Cancer Institute, Rotterdam, The Netherlands

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Thymoma and Thymic Carcinoma*

*DOI: http://dx.doi.org/10.5772/intechopen.87132*

ter and more treatment options in the future.

The lack of phase III level evidence due to the rarity of the disease calls for collaboration in research to improve the quality and impact of thymic malignancy treatment. Such efforts are currently underway, and hopefully this will lead to bet-

#### *Thymoma and Thymic Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.87132*

*Thymus*

carcinoma [21, 42, 67].

24 weeks [68].

**6.3 Follow-up**

been reported [70].

paraneoplastic syndromes.

**7. Conclusion**

classification.

some centers offer PORT (with or without chemotherapy) regardless of stage and resection margins [3, 21]. The available data is yet again limited, and there are indications that adjuvant therapy is not beneficial in R0-resected stage I thymic

chemotherapy in thymic carcinoma are even worse (4–12%) [55].

**Chemotherapy**. Thymic carcinomas respond less to chemotherapy than thymomas. Carboplatin/paclitaxel has the highest response rate in patients with thymic carcinoma, but even so this is only 22–36% [21, 55]. Response rates for second-line

**Checkpoint inhibitors**. Second-line treatment with pembrolizumab showed promising results in a phase II trial containing 40 patients with thymic carcinoma. There was an ORR of 22.5%, and the median duration of response was 22 months. While less in thymomas, there was still a high rate of immune-related adverse events (15%), including two cases of severe myocarditis [59]. A recently published study on nivolumab in thymic carcinoma patients showed no objective response in 15 patients, although 5 patients showed stable disease for more than

**Targeted therapies**. The same as in thymoma, experience with targeted therapies in thymoma is very limited and based on small phase II studies and individual case reports. Sunitinib may be beneficial for patients with a c-KIT mutation, although the mutation rate is rare <10% [10, 69]. IGFR inhibition and octreotide did not show any activity in thymic carcinoma, in contrast to thymomas [63, 64].

After primary resection, expert opinion on follow-up consists of a CT scan every 6 months for 2 years, then annually for 5 years for thymic carcinoma and annually for 10 years for thymomas [21], although an exceptional case of late recurrence has

Thymomas and thymic carcinomas are rare mediastinal tumors, and although the course of a thymoma can be indolent, they can indeed be locally invasive and metastasize. Thymic carcinomas more often are disseminated at presentation. Therefore, both are considered malignant. Forty to fifty percent of thymomas are related to autoimmune paraneoplastic syndromes, the most common being myasthenia gravis. Resection of the thymus can also act as treatment for the paraneoplastic syndrome. However, thymic treatment does not always resolve those

Because of the improved representation of the N-stage and correlation to prognosis, rather than surgical resectability, we recommend the AJCC eighth TMN

There is no phase III data available on the management of thymic epithelial tumors. Surgery is considered the cornerstone of thymoma and thymic carcinoma management in resectable disease and even in recurrent disease. Neoadjuvant treat-

In metastatic disease chemotherapy containing an anthracycline is advised. For recurrent metastatic disease sunitinib and octreotide, among other things, could be considered. A special note on checkpoint inhibitors should be made. Although they do show promising results in thymic carcinoma, the rate of immune-related adverse events is too high to consider this a valuable option for the treatment of thymoma

ment and PORT should be considered according to stage.

**84**

right now.

The lack of phase III level evidence due to the rarity of the disease calls for collaboration in research to improve the quality and impact of thymic malignancy treatment. Such efforts are currently underway, and hopefully this will lead to better and more treatment options in the future.


**Author details**

Kaushik Nag\*, Nabarun Karmakar and Anjan Datta Tripura Medical College and Dr BRAM Teaching Hospital, Agartala, India

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Importance of Geriatric Health Care in India during Covid 19 Pandemic DOI: http://dx.doi.org/10.5772/intechopen.95500*


**Author details**

A.B.M. Abdul Malek Department of Industrial and Production Engineering, Shahjalal University of Science and Technology, Sylhet, Bangladesh

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**3. Research method**

#### **3.1 Empirical setting**

This study was conducted at a hospital in the western part of Sweden. The health care produced at this hospital consists of both acute and planned health-care services, divided in three different medical areas, each of which is further subdivided into smaller units; 17 in total. Acute and planned health care respectively, call for

#### *Operations Knowledge Management in Health Care DOI: http://dx.doi.org/10.5772/intechopen.93793*

suitable for such knowledge-intensive organizations as health-care organizations [28]. In order to effectively create sustainable operations performance in health care, developments in knowledge capability is important [18, 21]. KM adds value to operations performance in organizations concerning cost, quality, flexibility, and delivery. Thus, knowledge is a strategically significant resource. KM can be viewed from two perspectives: process and infrastructure [21, 29, 30]. The process perspective reflects the capability in an organization, but the process is based and dependent on the infrastructure. The infrastructure perspective defines the technology, structure, culture, and mechanisms that enable the configuration of resources and operational routines in the organizational processes [21].

*Operations Management - Emerging Trend in the Digital Era*

Technology has made it easier to transmit information in organizations, and is an important part of the infrastructure [18]. Many sophisticated information systems are used within health care, and they have a tremendous impact on the complex organizational context. Information systems also include different structures of their own. Information systems thus create structures for how people perform their work, and how they interact with the systems [20, 31]. By understanding the complex relationships between the health-care organization and the information systems that are used, it is possible to get a better understanding of how information systems can support OM and KM [32]. However, effective communication and a shared interpretation of the knowledge are critical for the performance

Three mechanisms for KM practice systems have been identified by Loon [33]; (1) learning and knowledge creation culture; (2) organizational architecture for adaptive and exaptive capacity; and (3) "business model" for knowledge capitalization and value capture. *Learning and knowledge creation culture* is based on culture theories, in which learning is seen as a set of values among a group of professionals, which underpin their behavior in creating knowledge. Those values are shaped by organizational structures. This mechanism influences the importance placed on formal and informal learning in the organization, and includes reward schemes, coaching programs and other formalized KM-specific roles and operations that strengthen the learning and knowledge creation culture. The *organizational knowledge architecture for adaptive and exaptive capacity* consists of the design of organizational systems, technologies, practices, skills, and behaviors, that for example facilitate sharing of knowledge. This mechanism shapes the orientation of technology use, to primarily codify knowledge or to use technologies to connect people to exchange tacit knowledge. Appropriate and relevant structures, technologies, and processes have to be developed to allow knowledge to be stored, transformed, and exapted to facilitate the performance of the organization. The *business model for knowledge capitalization and value capture* describes how an organization benefits from its KM practice system. This mechanism is directing how new knowledge is embedded in the organization's value proposition, as the organization has to be aware of how newly created knowledge will be characterized as useful and appro-

This study was conducted at a hospital in the western part of Sweden. The health care produced at this hospital consists of both acute and planned health-care services, divided in three different medical areas, each of which is further subdivided into smaller units; 17 in total. Acute and planned health care respectively, call for

of a health-care organization.

priate for its outcomes and defined goals.

**3. Research method**

**3.1 Empirical setting**

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different planning methods. The patients' paths through the different health-care departments of the hospital is also planned and controlled, regardless of whether the health care is of an acute or planned character. The possibility for booking each patient is set by the detailed planning in each health-care department. To achieve a patient path that is as smooth and effective as possible, coordination of plans between different departments is often needed.

The mission, orders, and economical frames of Swedish hospitals are decided by the political governance. A document called "the health-care agreement" prescribes the overall assignments for the hospitals. This framework has to be transformed into terms that are useful for the planning and control processes within the hospitals, and communicated to the hospitals [20]. The admission of patients is also an important aspect that determines the need for resources and capacity. Moreover, there are databases of waiting lists with different patient groups, and different economical efforts at regional and national levels that affect the production of health care at the hospitals. Other regional health-care organizations, as well as the home health care conducted in the municipalities, also affect the production of health care at the hospitals.

At the studied hospital, the planning and control process generates forecasts, production plans, capacity plans, etc. The forecasts and plans aim to balance the needs for care within the frames given by the political governance. The different plans are then broken down through the organization, into more details regarding time horizons, care services, and resources at each department and service unit [20].

The processes of creating production plans differ to some extent between different levels in the organization. The collection of data and the elaboration of plans are performed by staff members with different positions in the organization. At the operations level, nurses often collect the data, create the plans, and book the patients. At the clinical department level, the manager and the production controller create the production plans. The plans cover one financial year and are adopted at the clinics board meetings once per year. At the hospital level, the production controllers from the different hospital departments together with the hospital's chief economic controller are responsible for creating the plans. The plans are adopted at the hospital board meeting once per year. The follow-up is normally done routinely each month, both at the levels of departments and hospital. Different actions are then taken when there are deviations from the defined production plans.