The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer A population‐based study of severity of comorbidity among patients with non‐Hodgkin's lymphoma: prognostic impact independent of International Prognostic Index Use of granulocyte colony-stimulating factor (G-CSF) in patients receiving myelosuppressive chemotherapy for the treatment of cancer. Provincial Systemic Treatment Disease Site Group. Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. Predictors of treatment failures during chemotherapy: A prospective study on 110 older cancer patients. Prevalence of Depression–PTSD Comorbidity: Implications for Clinical Practice Guidelines and Primary Care-based Interventions Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in breast cancer patients previously treated with paclitaxel. Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. Compliance and toxicity of adjuvant CMF in elderly breast cancer patients: a single-center experience Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. Influence of Alternative Thresholds for Initiating HIV Treatment on Quality-Adjusted Life Expectancy: A Decision Model Oral Etoposide in Elderly Patients with Advanced Non Small Cell Lung Cancer: A Clinical and Pharmacological Study Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy. Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer. How old is old: the beginning of a new era for therapeutic challenges for elderly patients with AML Colorectal Cancer Screening in the Elderly: The Need for Informed Decision Making Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study Adjuvant capecitabine chemotherapy using a tailored-dose strategy in elderly patients with colon cancer. Dose ranging evaluation of the antiemetic efficacy and toxicity of intramuscular levonantradol in cancer subjects with chemotherapy-induced emesis. Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. On and off Metronomic Oral Vinorelbine in Elderly Women with Advanced Breast Cancer Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: a phase II randomized trial Lung cancer chemotherapy decisions in older patients: the role of patient preference and interactions with physicians Prognostic importance of comorbidity in a hospital-based cancer registry. Economic Analysis of Gene Expression Profile Data to Guide Adjuvant Treatment in Women with Early-Stage Breast Cancer Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. Predictors of the course of quality of life during therapy in women with primary breast cancer Knowledge of Efficacy of Treatments in Lung Cancer Is Not Enough, Their Clinical Effectiveness Should Also Be Known Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.
R and omized controlled trials ( RCTs ) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment . For many patients , cancer is a chronic illness ; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making , as “ concrete ” patient outcomes ( eg , survival ) will likely be excellent independent of the intervention , and detecting a difference between trial arms may be impossible . In this commentary , we articulate 9 recommendations that we hope future clinical trialists and funding agencies ( including those under the National Cancer Institute ) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making , based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men , that is , prostate cancer . We recommend routinely reporting : ( 1 ) race ; ( 2 ) medical comorbidities ; ( 3 ) psychiatric comorbidities ; ( 4 ) insurance status ; ( 5 ) education ; ( 6 ) marital status ; ( 7 ) income ; ( 8) sexual orientation ; and ( 9 ) facility-related characteristics ( eg , number of centers involved , type of facilities , yearly hospital volumes ) . We discuss how these factors independently affect patient outcomes and toxicities ; future clinicians and governing organizations should consider this information to plan RCTs accordingly ( to maximize patient accrual and total n ) , select appropriate endpoints ( eg , toxicity , quality of life , sexual function ) , actively monitor RCTs , and report results so as to identify the optimal treatment among sub population Over 60 % of patients aged over 70 years , diagnosed with non‐Hodgkin 's lymphoma ( NHL ) in the Netherl and s have serious comorbidity . We studied the independent influence of comorbidity on choice of treatment , dose reductions , treatment‐related toxicity and prognosis , using data from a r and om sample of 381 patients from the population ‐based Eindhoven Cancer Registry . About 45 % of patients over 60 years of age with NHL had high impact comorbidity at the time of cancer diagnosis . The proportion of patients with aggressive NHL who received chemotherapy  decreased from 85 % in patients aged 40–60 years to 70 % in those over 60 years . About 65 % of systematic ally treated patients with aggressive NHL suffered from treatment‐related toxicity . Toxicity appeared to be more common among females and those with high‐intermediate or high International Prognostic Index ( IPI ) risk . Among patients with aggressive NHL , the chance of dying for those with high impact comorbidity was twice as high compared with those without comorbidity . This was independent of the IPI risk . Dose reductions are frequently unavoidable for patients with severe comorbidity , poor performance status or chemotherapy‐related toxicity . Whether the less frequent prescription of ( full dose ) chemotherapy for patients with advanced age and /or with comorbidity is justified remains a question for debate GUIDELINE QUESTIONS 1 ) Does G-CSF reduce the incidence of important adverse clinical outcomes due to infections in patients with cancer treated with myelosuppressive therapy ? 2 ) Does G-CSF allow maintenance of the chemotherapy dose with the goal of improving survival ? OBJECTIVE To evaluate the evidence for the role of G-CSF in patients receiving myelosuppressive chemotherapy for the treatment of cancer . OUTCOMES Clinical outcomes reflecting events that may affect quality of life and /or re source utilization ( e.g. , rates and duration of hospitalization , antibiotic use ) ; outcomes reflecting the effect of treatment on infection rates , tumour response and survival and those related to the biological effect of G-CSF . PERSPECTIVE ( VALUES ) Evidence was selected , review ed and synthesized by members of the Provincial Systemic Treatment Disease Site Group ( DSG ) of the Cancer Care Ontario Practice Guidelines Initiative . Drafts of this document have been circulated and review ed by members of the Systemic Treatment DSG . The DSG comprises medical oncologists , pharmacists , supportive care personnel and administrators . Evaluation by clinicians was considered in the final practice guideline . Community representatives did not participate in the development of this report but will in future reports . Guidelines approval does require participation by community representatives . QUALITY OF EVIDENCE Two published guidelines and an up date of one guideline were identified . Ten eligible r and omized controlled trials published in English were included . BENEFITS A meta- analysis of data from 8 trials showed that the odds of experiencing febrile neutropenia with G-CSF were significantly reduced ( odds ratio 0.38 ; 95 % confidence interval [ CI ] 0.27 to 0.52 ; p < 0.00001 ) . G-CSF reduced the risk of febrile neutropenia by 34 % ( risk ratio 0.66 ; 95 % CI 0.51 to 0.86 ; p = 0.0015 ) . The use of G-CSF was associated with a significant reduction in antibiotic usage and days spent in hospital in 2 trials and had no effect in the other 4 in which it was measured . Five trials reported no difference in overall median survival , with 2 small trials detecting a significant increase related to G-CSF . However , further research is necessary to confirm these results . HARMS The toxic effects of G-CSF are relatively mild . The most consistent clinical symptom attributed to G-CSF is bone pain , reported in incidence rates ranging from 20 % to 50 % in 3 trials . Except for one case , reported bone pain was mild . PRACTICE GUIDELINE In cancer patients receiving myelosuppressive chemotherapy , granulocyte colony-stimulating factor ( G-CSF ) may be beneficial for some patients . If a reduction in the number of febrile neutropenic episodes , or in the duration of such episodes , is expected to improve quality of life , then G-CSF is a reasonable treatment option for selected patients . A clear justification for the use of G-CSF should be stated . If the objective of using G-CSF is to maintain dose intensity of antitumour agents , then G-CSF can be recommended where reduction in dose intensity has been shown in r and omized controlled trials to reduce survival or disease-free survival . Although the evidence is weaker , the Systemic Treatment DSG would support the practice endorsed by other guidelines ( American Society of Clinical Oncology , Ontario Drug Benefit Plan ) and would recommend G-CSF for patients receiving potentially curative chemotherapy : i ) as primary prophylaxis ; that is , where dose reductions below a specified level are required because of a known high risk of febrile neutropenia , or ii ) as secondary prophylaxis in patients receiving chemotherapy of established efficacy who have suffered a prior serious episode of febrile neutropenia due to the same chemotherapy regimen . The exact cut-off for dose reductions is unknown at this time and ought to be left to the judgement of the clinician . In general , the use of  G-CSF  for dose reductions lower than 20 % is not recommended . ( ABSTRACT TRUNCATED PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer . METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology , radiation oncology , surgical oncology , gastroenterology , palliative care , and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015 . Outcomes included overall survival , disease-free survival , progression-free survival , and adverse events . RESULTS Twenty-six r and omized controlled trials met the systematic review criteria . RECOMMENDATIONS A multiphase computed tomography scan of the chest , abdomen , and pelvis should be performed . Baseline performance status and comorbidity profile should be evaluated . The goals of care , patient preferences , psychological status , support systems , and symptoms should guide decisions for treatments . A palliative care referral should occur at first visit . Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile . There is no clear evidence to support one regimen over another . The gemcitabine-based combinations and treatments recommended in the metastatic setting ( eg , fluorouracil , leucovorin , irinotecan , and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel ) have not been evaluated in r and omized controlled trials involving locally advanced , unresectable pancreatic cancer . If there is local disease progression after induction chemotherapy , without metastasis , then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile . If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities , radiation therapy may be offered as an alternative . Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline . Follow-up visits every 3 to 4 months are recommended . Additional information is available at www.asco.org/ guidelines /LAPC and www.asco.org/ guidelines /MetPC and www.asco.org/ guidelines wiki PURPOSE Surgical resection is st and ard therapy in stage I non-small-cell lung cancer ( NSCLC ) ; however , many patients are inoperable due to comorbid diseases . Building on a previously reported phase I trial , we carried out a prospect i ve phase II trial using stereotactic body radiation therapy ( SBRT ) in this population . PATIENTS AND METHODS Eligible patients included clinical ly staged T1 or T2 ( < or = 7 cm ) , N0 , M0 , biopsy-confirmed NSCLC . All patients had comorbid medical problems that precluded lobectomy .  SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks . RESULTS All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months . The 3-month major response rate was 60 % . Kaplan-Meier local control at 2 years was 95 % . Altogether , 28 patients have died as a result of cancer ( n = 5 ) , treatment ( n = 6 ) , or comorbid illnesses ( n = 17 ) . Median overall survival was 32.6 months and 2-year overall survival was 54.7 % . Grade 3 to 5 toxicity occurred in a total of 14 patients . Among patients experiencing toxicity , the median time to observation was 10.5 months . Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83 % compared with only 54 % for patients with central tumors . CONCLUSION High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC . Both local recurrence and toxicity occur late after this treatment . This regimen should not be used for patients with tumors near the central airways due to excessive toxicity Several instruments have been proposed to improve treatment decisions in elderly cancer patients , but evidence of their impact in clinical practice is limited . The aim of this study was to analyze the role of clinical and functional factors in predicting serious adverse events , including death , severe toxicity or treatment interruption , during chemotherapy in elderly cancer patients . The survey evaluated elderly with lung or colon or breast cancer treated with chemotherapy , followed by S. Giovanni Battista Hospital . We enrolled 110 consecutive patients older than 70 years of age with lung ( n=45 ) , colon ( n=50 ) and breast ( n=15 ) cancer between October 2004 and October 2005 . Overall , 73/110 patients ( 66.4 % ) experienced adverse events as death ( n=14 ) , grade s III and IV toxicity ( n=40 ) , or treatment interruption for other reasons ( n=19 ) . The variables with stronger predictivity were advanced stage , toxicity of treatment , level of comorbidity and Karnofsky performance status ( KPS ) . instrumental activities of daily living ( IADL ) index and age itself were not independent predictors . In conclusion our results confirm the need of a careful selection of elderly patients suitable for chemotherapy  , giving more weight to comorbidity and KPS scores than to age itself . The potential role of other functional evaluations need to be further assessed in r and omized controlled trials BACKGROUND Compared to those with depression alone , depressed patients with posttraumatic stress disorder ( PTSD ) experience more severe psychiatric symptomatology and factors that complicate treatment . OBJECTIVE To estimate PTSD prevalence among depressed military veteran primary care patients and compare demographic/illness characteristics of PTSD screen-positive depressed patients ( MDD-PTSD+ ) to those with depression alone ( MDD ) . DESIGN Cross-sectional comparison of MDD patients versus MDD-PTSD+ patients . PARTICIPANTS Six hundred seventy-seven r and omly sample d depressed patients with at least 1 primary care visit in the previous 12 months . Participants composed the baseline sample of a group r and omized trial of  collaborative care for depression in 10 VA primary care practice s in 5 states . MEASUREMENTS The Patient Health Question naire-9 assessed MDD . Probable PTSD was defined as a Primary Care PTSD Screen ≥ 3 . Regression-based techniques compared MDD and MDD-PTSD+ patients on demographic/illness characteristics . RESULTS Thirty-six percent of depressed patients screened positive for PTSD . Adjusting for sociodemographic differences and physical illness comorbidity , MDD-PTSD+ patients reported more severe depression ( P < .001 ) , lower social support ( P < .001 ) , more frequent outpatient health care visits ( P < .001 ) , and were more likely to report suicidal ideation ( P < .001 ) than MDD patients . No differences were observed in alcohol consumption , self-reported general health , and physical illness comorbidity . CONCLUSIONS PTSD is more common among depressed primary care patients than previously thought . Comorbid PTSD among depressed patients is associated with increased illness burden , poorer prognosis , and delayed response to depression treatment . Providers should consider recommending psychotherapeutic interventions for depressed patients with PTSD e20505 Background : Neuropathic pain ( NP ) remains difficult to control for a significant proportion of patients with cancer . Chemotherapy induced peripheral neuropathy ( CIPN ) is postulated as an initial stage to the development of NP . Among breast cancer patients , taxanes , platinum agents , and vinca alkaloids are most likely to cause NP . The purpose of this study was to assess the extent to which those who experienced CIPN ( NCI toxicity criteria ≥ grade 2 sensory neuropathy ) during paclitaxel chemotherapy were at risk of developing chronic NP , controlling for disease- and treatment-related variables ( e.g. , stage of disease , location of tumor chemotherapy and other cancer therapies , dose of chemotherapy and duration of treatment ) , clinical health status ( e.g. , comorbid conditions ) , and sociodemographic characteristics ( e.g. , age , race ) . METHODS We conducted a follow-up survey of breast cancer patients who previously participated in clinical trials for paclitaxel .  Patients were asked if they have ever been diagnosed by the physician or healthcare provider for NP during the survey . Clinical trial data ( NCI Toxicity , cummulative dose ) were abstract ed from a clinical data base . RESULTS Of the 430 potential respondents , 240 responded to the survey . Mean follow-up time was 9.5 years ( SD=2.1 ) . Sixty three percent of the respondents had grade 2 or greater sensory neuropathy during their previous treatment with paclitaxel . Follow-up data showed that 18 % ( 43/240 ) were subsequently diagnosed by their physician to have NP . Logistic regression analysis showed that those with CIPN during the trial were 3 times more likely to having been diagnosed with NP ( OR=3 ; 95%CI=1.2 ; 7.2 ; p<0.001 ) , which persisted in the multivariable model . Other variables found to be associated with NP included cummulative dose of paclitaxel , and comorbid conditions such as diabetes and osteoarthritis . Patients with NP reported twice as many visits to their health care provider ( p=0.028 ) ; had taken more prescription ( 50 % versus 19 % ; p=0.0001 ) for pain relative to those without NP . CONCLUSIONS We provide empirical evidence on the importance CIPN as a risk factor for NP in breast cancer patients . Prospect i ve studies with larger cohorts are needed to vali date our findings . No significant financial relationships to disclose PURPOSE This study analyzed patients enrolled in two large , prospect ively r and omized trials of systemic chemotherapy ( adjuvant/palliative setting ) for non-small-cell lung Cancer ( NSCLC ) . The main objective was to determine if age and /or the burden of chronic medical conditions ( comorbidity ) are independent predictors of survival , treatment delivery , and toxicity . PATIENTS AND METHODS Baseline comorbid conditions were scored using the Charlson comorbidity index ( CCI ) , a vali date d measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality . The CCI score ( CCIS ) was correlated with demographic data , ( ie , age , sex , race ) , performance status ( PS ) , histology , cancer stage , patient weight , hemoglobin , alkaline phosphatase , lactate dehydrogenase , outcomes of chemotherapy delivery ( ie , type , total dose , and dose intensity ) , survival , and response . RESULTS A total of 1,255 patients were included in this analysis . The median age was 61 years ( range , 34 to 89 years ) ; 34 % of patients were elderly ( at least 65 years of age ) ; and 31 % had comorbid conditions at r and omization . Twenty-five percent of patients had a CCIS of 1 , whereas 6 % had a CCIS of 2 or greater . Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients ( 42 % v 26 % ; P < .0001 ) , as were male patients ( 35 % v 21 % ; P < .0001 ) and patients with squamous histology ( 36 % v 29 % ; P = .001 ) . Although age did not influence overall survival , the CCIS appeared prognostic ( CCIS 1 v 0 ; hazard ratio 1.28 ; 95%CI , 1.09 to 1.5 ; P = .003 ) . CONCLUSION In these large , r and omized trials , the presence of comorbid conditions ( CCIS > or = 1 ) , rather than age more than 65 years , was associated with poorer survival Background Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients ;  CMF ( cyclophosphamide , methotrexate , fluorouracil ) can be reasonably considered the most widely accepted st and ard of treatment . Methods We retrospectively review ed compliance and safety of adjuvant CMF in patients older than 60 . The treatment was indicated if patients had no severe comorbidity , a high-risk of recurrence , and were younger than 75 .  Toxicity was coded by NCI-CTC . Toxicity and compliance were compared between two age subgroups ( < 65 , ≥ 65 ) by Fisher exact test and exact Wilcoxon rank-sum test . Results From March 1991 to March 2002 , 180 patients were identified , 100 older than 60 and younger than 65 , and 80 aged 65 or older . Febrile neutropenia was more frequent among older patients ( p = 0.05 ) . Leukopenia , neutropenia , nausea , cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies , while mucositis tended to be more evident among younger patients , all not significantly . Almost one half ( 47 % ) of the older patients receiving concomitant radiotherapy experienced grade 3–4 haematological toxicity . Compliance was similar in the two groups , with 6 cycles administered in 86 % and 79 % , day-8 chemotherapy omitted at least once in 36 % and 39 % , dose reduction in 27 % and 38 % , prolonged treatment duration ( ≥ 29 weeks ) in 10 % and 11 % and need of G-CSF in 9 % and 18 % , among younger and older patients , respectively . Conclusion Our data show that , in a highly selected population of patients 65 or more years old , CMF is as feasible as in patients older than 60 and younger than 65 , but with a relevant burden of toxicity . We suggest that prospect i ve trials in elderly patients testing less toxic treatment schemes are m and atory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence PURPOSE To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative ( or unknown ) advanced breast cancer . METHODS A systematic review of r and omized evidence ( including systematic review s and meta-analyses ) from 1993 through to current was completed . Outcomes of interest included survival , progression-free survival , response , quality of life , and adverse effects . Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus . RESULTS Seventy-nine studies met the inclusion criteria , comprising 20 systematic review s and /or meta-analyses , 30 trials on first-line treatment , and 29 trials on second-line and subsequent treatment . These trials form the evidence base for the guideline recommendations . RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) . Single agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity . There is no single optimal first-line or subsequent line chemotherapy , and choice of treatment will be determined by multiple factors including prior therapy , toxicity , performance status , comorbid conditions , and patient preference . The role of bevacizumab remains controversial . Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer Context Trials have not answered questions about optimal timing of HIV therapy , and many benefits and harms of therapy occur over time horizons that are longer than the trials . Early treatment may postpone AIDS , but it may also increase resistance and unnecessarily subject patients to the costs and toxicity of drugs . Contribution This computer simulation estimated that starting treatment earlier ( CD4 count threshold of 500 cells/mm3 ) would provide greater unadjusted and quality -adjusted life expectancy than starting it later ( at a CD4 count of 350 or 200 cells/mm3 ) for all patients age 30 years and for patients age 40 years who have a viral load greater than 30000 copies/mL. Caution Increases in life expectancy were small , and the analysis did not consider costs . The Editors The optimal timing for initiating HIV treatment has long been controversial . Soon after combination antiretroviral therapies became available , the prevailing treatment ethos was hit early , hit hard , and patients often began receiving therapy immediately after HIV infection was diagnosed ( 1 ) . However , as it became clear that toxicity and side effects from combination antiretroviral therapy were substantial ( 25 ) and that early treatment may hasten genotypic resistance ( 68 ) , treatment guidelines increasingly have favored postponing therapy initiation ( 9 , 10 ) . Yet , postponing therapy has disadvantages because it exposes HIV-infected patients to a greater risk for AIDS than is otherwise necessary ( 915 ) and may impair immune reconstitution ( 16 ) . Guidelines once again may be in flux , trending toward earlier treatment initiation ( 17 ) . The controversy about when to initiate HIV treatment has persisted because it has been difficult to systematic ally and quantitatively weigh the benefits and harms of earlier treatment ( 17 ) . Furthermore , because benefits and harms may be delayed ( for example , the accrual of genotypic resistance ) ( 8) , they must be estimated over time horizons that exceed usual follow-up periods for clinical trials . Mathematical models offer the possibility of quantitatively weighing harms and benefits over long time horizons , and therefore have theoretical promise for informing this question . However , published mathematical models addressing this question have not considered toxicity , side effects , and accrual of resistance mutations , the primary risks of earlier treatment initiation ( 1821 ) . Furthermore , they have not considered how the balance of risks to benefits may vary with advancing age because of changes in antiretroviral toxicity or immune reconstitution . For these reasons , we incorporated toxicity and side effects of combination antiretroviral therapy  into our previously vali date d HIV computer simulation , which considers resistance mutations and their likelihood of causing premature antiretroviral failure ( 2224 ) . We used the simulation to evaluate how these tradeoffs influence the optimal time to initiate therapy . Methods We first describe how we quantified the potentially harmful consequences of combination antiretroviral therapy and then discuss how we incorporated these estimates into our HIV simulation . Estimating the Harmful Consequences of Combination Antiretroviral Therapy We partitioned the harmful effect of combination antiretroviral therapy into 2 quantifiable categories : 1 ) a harmful effect on quantity of life due to toxicity and amplified risks for common comorbid events ( for example , myocardial infa rct ion ) ( 25 ) , manifested by higher nonHIV-related mortality and 2 ) a harmful effect on quality of life due to side effects , manifested by decreased scores on a preference-based quality -of-life measure ( 25 ) . Estimating the Effect of Combination Antiretroviral Therapy on NonHIV-Related Mortality It is not possible to directly estimate the effect of combination antiretroviral therapy on nonHIV-related mortality because there has been no r and omized , controlled trial with requisite statistical power . Large observational cohorts of HIV-infected patients have ample statistical power to address this question by comparing nonHIV-related mortality among individuals receiving with those not receiving combination antiretroviral therapy . However , confounding by treatment assignment may bias these results substantially , and the direction of this bias may be unclear . We therefore conducted our own analysis of mortality among all HIV-infected individuals receiving care within the Veterans Health Administration nationwide , together with a sample of uninfected Veterans Health Administration controls , matched 2:1 by age , race , and site . This virtual cohort includes in patients as well as out patients and patients receiving subspecialty care as well as those receiving primary care . It was created by integrating data from pharmacy , laboratory , and administrative sources from 1997 through 2004 . The creation of this virtual cohort is described in detail elsewhere ( 26 ) and has been shown to identify HIV-infected veterans with a sensitivity of 90 % and a specificity of 99.9 % ( 26 ) . We limited our analysis to HIV-infected individuals who were receiving combination antiretroviral therapy ( 3 drugs ) and were at exceptionally low risk for HIV-related death . We then compared the mortality of HIV-infected patients who met these inclusion criteria with that of their matched uninfected controls . Our rationale in making this comparison was that excess mortality observed in the HIV-infected group could be viewed as an upper limit for the nonHIV-related mortality attributable to combination antiretroviral therapy because it would reflect nonHIV-related mortality as well as other factors ( for example , residual mortality attributable to HIV ) . We decided not to analyze only HIV-infected patients because we did not think that we could fully control for intention-to-treat bias and because we would not know the direction of this bias ( that is , we would not know that the result was accurate or that it bounded the true value in a particular direction ) . We selected individuals at low risk for death related to HIV by specifying a minimum threshold for their time-up date d CD4 count ( that is , individuals could contribute a particular interval of observation to the analysis only if they remained above the CD4 count threshold during that interval ) . We used a threshold of 500 cells/mm3 because it is uncommon for individuals with higher CD4 counts to die of an AIDS-related cause ( 27 ) . We also explored alternative analyses using thresholds based on minimum CD4 count rather than time-varying CD4 count ( 9 ) , but this did not affect our results substantially . We performed Cox proportional hazards models to compare the mortality of the HIV-infected patients with that of their matched uninfected controls , including the covariates age , sex , race , site of care , and presence or absence of the most common serious comorbid conditions in this sample ( coronary artery disease , congestive heart failure , diabetes mellitus , hepatitis C , pancreatitis , peripheral vascular disease , pulmonary disease , stroke , pneumonia , and non-AIDS cancer ) . Diagnoses were identified by using a previously vali date d algorithm based on International Classification of Diseases , Ninth Revision , administrative codes in the inpatient and outpatient setting s ( 26 ) . To avoid overadjusting for comorbid conditions , we required comorbidity diagnoses to have been made before combination antiretroviral therapy was initiated . We did not stratify combination antiretroviral therapy by type ( for example , regimens with protease inhibitors versus regimens with nonnucleoside reverse transcriptase inhibitors ) because this would have greatly limited our statistical power . Because there appeared to be a substantially higher mortality hazard in the short term after the start of combination antiretroviral therapy ( during the first 3 months ) than over the long term , we considered this short-term hazard separately . We judged this high short-term hazard as probably due to confounding ( that is , attributable to an acute clinical syndrome that may have prompted the initiation of care ) rather than to combination antiretroviral therapy toxicity , and therefore we did not incorporate it into the simulation 's base-case analysis . However , we also explored alternative analyses in which we did attribute this high short-term hazard to toxicity , and this did not affect our results substantially . Among 33420 HIV-infected patients in the virtual cohort , 9633 ( 29 % ) had infrequent or missing CD4 counts ( > 1 year between successive CD4 measurements ) , and an additional 18045 did not meet inclusion criteria ( no combination antiretroviral therapy , or CD4 count always < 500 cells/mm3 ) , leaving 5742 HIV-infected patients along with 11484 controls ( 17226 patients in total ) in our analysis . The mean age of patients and controls was 45.7 years , 98.0 % were men , and 68.9 % were nonwhite . We found that combination antiretroviral therapy was associated with a 3.4-fold increased long-term hazard of nonHIV-related mortality in unadjusted analyses ( 95 % CI , 2.8-fold to 4.1-fold ) and a 3.8-fold increased hazard in adjusted analyses ( CI , 3.1-fold to 4.6-fold ) ( Table 1 ) . Because this association is likely to encompass factors other than toxicity of combination antiretroviral therapy , it is an upper-bound estimatethat is , the true magnitude of the effect of combination antiretroviral therapy is likely to be lower . We included this estimate in the simulation model with the underst and ing that it biases the model in a known , conservative direction ( against showing a benefit from earlier treatment initiation ) . Table 1 . Analysis to Estimate Upper Bound for Mortality from Therapy-Related Toxicity : Predictors of Mortality among HIV-Infected Veterans and Matched Uninfected Controls Nationwide in the Veterans Affairs Health System * Estimating the Effect of Combination Antiretroviral Therapy on Quality of Life We estimated the effect of combination antiretroviral therapy on quality of life Abstract Seventeen elderly patients with advanced progressive non small cell lung cancer ( NSCLC ) were treated with oral etoposide at the daily dose of 100 mg for 14 days every 3 - 4 weeks with pharmacokinetic monitoring . One partial response and 6 stabilizations were documented with a median overall duration of 13 weeks ( range 8 - 32 ) . The median survival was 24 weeks with an apparent advantage for non-progressive patients ( 40 weeks vs. 18 weeks ) . The treatment was well tolerated especially by those patients without concomitant illness , suggesting the crucial role of a careful selection of the geriatric population . Toxicity was not related to the etoposide plasma level , but was clearly dependent on comorbidity . A geriatric assessment rather than chronological age therefore appears to be more reliable in the selection of elderly patients for clinical trials . The easy self-management , favorable toxicity profile and synergy with other compounds makes oral etoposide suitable for further clinical -pharmacological studies in elderly patients AIM OF THE STUDY To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer ( NSCLC ) have a shorter overall survival , experience more toxicity or more deterioration of health-related quality of life ( HRQoL ) than other patients during treatment . PATIENTS AND METHODS Patients enrolled onto a phase III trial comparing pemetrexed/carboplatin with gemcitabine/carboplatin as first-line therapy of stage IIIB/IV NSCLC were analysed . Eligible patients had performance status 0 - 2 and adequate kidney/liver/bone-marrow function .  Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics ( CIRS-G ) . Toxicity was grade d using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire (QLQ)-C30/LC13 . RESULTS Data from 402 of the 436 of the patients enrolled onto the phase III trial were analysed . The patients with severe comorbidity had similar survival as other patients ( 6.9 versus 8.1months ; p=.34 ) , similar frequency of neutropenia ( 48 % versus 42 % ; p=.16 ) , but experienced more neutropenic fevers ( 12 % versus 5 % ; p=.012 ) and deaths from neutropenic infections ( 3 % versus 0 % ; p=.027 ) . They had more thrombocytopenia ( 46 % versus 36 % ; p=.03 ) , but not more thrombocytopenic bleedings ( 3 % versus 4 % ; p=.65 ) . In general , the patients with severe comorbidity reported poorer HRQoL , but not significantly more deterioration of HRQoL. CONCLUSIONS The results from our study suggest that patients with advanced NSCLC who have severe co-existing disorders benefit from and tolerate platinum-doublet chemotherapy as well as other patients . They do , however , appear to have a higher risk of acquiring infections when neutropenic PURPOSE / OBJECTIVES To examine the relationships among pain , fatigue , insomnia , and gender while controlling for age , comorbidities , and stage of cancer in patients newly diagnosed with lung cancer within 56 days of receiving chemotherapy .  DESIGN Secondary data analysis . SETTING Accrual from four sites : two clinical community oncology programs and two comprehensive cancer centers . SAMPLE 80 patients newly diagnosed with lung cancer . METHODS Analysis from baseline observation of a r and omized clinical intervention trial . Multinomial log-linear modeling was performed to explain the relationships among pain , fatigue , insomnia , and gender . MAIN RESEARCH VARIABLES Pain , fatigue , insomnia , and gender . FINDINGS For all people with lung cancer , fatigue ( 97 % ) and pain ( 69 % ) were the most frequently occurring symptoms ; insomnia occurred 51 % of the time . A model containing all main effects ( two-way interactions of pain and fatigue , pain and insomnia , and insomnia and gender ; and the three-way interaction of pain , fatigue , and insomnia , along with three covariates [ age , comorbidities , and stage of cancer ] ) was a good fit to the data . Parameter estimates indicated that a statistically significant effect from the model was the three-way interaction of pain , fatigue , and insomnia . Gender did not make a difference . Age , comorbidities , and stage of cancer were not significant covariates . CONCLUSIONS For people newly diagnosed with lung cancer undergoing chemotherapy  , multiple symptoms occur simultaneously rather than in isolation ; a symptom cluster exists , consisting of pain , fatigue , and insomnia ; and no relationship was found among gender , pain , fatigue , and insomnia . IMPLICATION S FOR NURSING By underst and ing this symptom cluster , healthcare providers can target specific troublesome symptoms to optimize symptom management and achieve the delivery of high- quality cancer care When patients with acute myeloid leukemia ( AML ) relapse , prognosis is considered dismal , even if the patient experiences a long period of complete remission ( CR ) . Although we live in an era of genomic and epigenomic information , the management of elderly Korean patients with AML remains a challenge , given the patient 's age , poor performance status , and various pre-existing comorbidities . As we know , the incidence of AML increases sharply with age , especially after the age of 55 . According to the Surveillance , Epidemiology , and End Results ( SEER ) data ( 2006 - 2010 ) , almost 70 % of AML patients are > 55 years old , with the peak incidence occurring at > 75 years [ 1 , 2 , 3 ] . Unfortunately , most elderly AML patients do not receive intensive therapies , due to their age , a pattern that is based on the common misconception that elderly patients can not tolerate chemotherapies . US SEER data from 2000 - 2007 revealed that only one third of elderly AML patients received early chemotherapy after initial diagnosis [ 2 ] , although no Korean data exists to date . However , higher comorbidities and poor performance status , have a greater negative impact than age per se . Although there have been no large efficacy trials for these patients , large registry data , in addition to some positive retrospective studies , have shown that intensive induction therapy can improve survival [ 4 , 5 , 6 ] . There are currently many ongoing trials for selected elderly AML patients , including some with post-CR allogeneic hematopoietic stem cell transplantation ( alloHSCT ) approaches . However , a well design ed treatment for elderly AML patients should be examined prospect ively to determine whether patients who receive less toxic therapies achieve CR , whether post-CR alloHSCT may be avoided , and whether a true cure can be found with recent novel therapeutic agents . In the present issue of Blood Research , Yi et al. [ 7 ] found that carefully selected elderly Korean AML patients ( median age 70 years ) experienced beneficial effects after treatment with either high-intensity regimens ( HIR ) or low-intensity regimens ( LIR ) . The authors found that the median survival periods with HIR and LIR  were 6.8 and 10.2 months , respectively , compared to just 1.6 months for patients who only received supportive care ( SC ) . Multivariate analysis of the 168 patients , diagnosed in five institutes , identified age , ECOG performance status , Hb level , and serum creatinine at diagnosis as statistically significant prognostic factors for survival . Given the low sample numbers in the study , the authors suggested that further prospect i ve trials would be necessary to identify specific prognostic factors , which could be used to precisely characterize elderly Korean AML patients . However , some limitations in the study , and particularly some novel aspects that are presented should be noted . Firstly , the conclusion that HIR ( N=76 ) provides an inferior median survival to LIR ( N=18 ) ( 6.8 months vs. 10.2 months ) is based on a very small sample size , and may not be supported by the study results . The CR rate in the LIR group was just 5.6 % , compared to 42.9 % in the HIR group , which may suggest that the LIR group had been drawn from antiquated trials of uncertain design . Although LIR may contain various dose-intensity schedules , the overall median survival of 10.2 months for AML patients > 65 years old is not a disappointing result , especially when compared with many older studies , or even recent therapeutic trials with novel agents [ 8 ] . Therefore , this date d treatment method should be amended , so as not to create confusion in a field clouded by lack of consensus . The authors also state that CR rates in the favorable , intermediate , and unfavorable groups were 20.0 % , 22.6 % , and 21.8 % respectively . However , it is useless to comment on the risk grouping in this study , if the categorization was solely dependent on conventional cytogenetics , without molecular parameters . Although elderly AML patients receiving only SC ( N=66 ) had a survival of 1.6 months , there was a prolonged survival for patients who received either HIR or LIR . However , these patients did not receive further intensive stem cell transplantation after achieving CR , since the extremely elderly patient ( > 65 years ) were considered unable to maintain continuous CR and were unable to obtain reimbursement for alloHSCT in Korea . Secondly , the 168 patients diagnosed at Gyeonggi area hospitals did not accurately represent elderly Korean patients with AML . As well , the four parameters from the analytic prognostic factors in this study do not accurately represent Korean patients either . Lastly , the continuous improvements of treatment regimens , through the introduction of epigenetic modulators in the 21st century , along with post-CR alloHSCT with reduced toxicity conditioning , should have been investigated , since even patients aged 65 - 75 years have exhibited encouraging results . Instead of the multivariate analyses performed on all patients , or on the HIR , I recommend other productive conclusions after examining the data . The study included only 168 patients , diagnosed at local Korean institutes , where there are simply too many confounding variables to be considered in each facility . However , recent therapeutic reports for elderly Korean AML patients note that regimens containing low-dose cytosine arabinoside or mylotarg had similar superior outcomes , when compared to conventional intensive care patients [ 9 , 10 ] . These results are especially notable for low-risk groups after considering multiple parameters , including comorbidity score , ECOG performance status , and age . Similarly , Yi et al. [ 7 ] found that age , ECOG performance status , Hb level , creatinine level , and C-reactive protein ( CRP ) level at initial diagnosis were considered prognostic factors . Although their study , as a pilot retrospective investigation , contains weaknesses , further prospect i ve studies with well-selected patients could result in much improved outcomes for elderly Korean AML patients . I suggest that reliable prognostic and /or predictive factors should be used for approaching intensive therapies , including the use of elective alloHSCT after CR . Although age has been considered one of the most important risk factors in most historical studies , tailor-made therapies , based on well- design ed clinical trials with quality of life considerations , should be used to define the appropriate multimodality for current therapeutic options . The concept that AML patients older than 65 or 70 years can not achieve CR should be rejected , since some patients possess favorable molecular cytogenetic profiles , allowing them to maintain continuous CR through treatment with only low-dose cytosine arabinoside or hypomethylating agents in outpatient clinic . We are still faced with the unresolved old-age AML management hurdles , especially for true elderly patients aged over 70 - 75 years . Therefore , it is imperative that we develop more reasonable treatment strategies for aging Korean AML patients in the near future . Again , how old is old Colorectal cancer screening works ! We have convincing evidence from r and omized trials of fecal occult blood tests ( FOBT ) showing that colorectal cancer screening reduces disease-specific morbidity and mortality1 . Case-control studies suggest that endoscopy is also effective2–4 . Nonetheless , only about 60 % of eligible adults are currently screened for colorectal cancer5 . In contrast , nearly 75 % of women are currently screened for breast cancer6 , which has a similar level of evidence for efficacy as colorectal screening . More than 70 % of men are currently screened for prostate cancer , which has uncertain efficacy7 . The discordance between evidence and uptake of colorectal cancer screening has sparked considerable efforts to increase screening rates . However , the report by Kahi and colleagues suggests that these efforts may have the unintended consequence of promoting screening recommendations that fail to adequately consider the risks and benefits of screening in the context of a patient′s health status and life expectancy8 . Perhaps cancer screening is like the forward pass in football . Darrell Royal the legendary coach at the University of Texas has said , “ When you throw a pass , only three things can happen , and two of ‘ em are bad . ” Colorectal cancer screening can reduce morbidity and mortality , the supreme accomplishment of a screening program . However , the absolute benefit to a screened population is small ; most people will not benefit because they do not have early-stage colorectal cancer or polyps destined to become malignant . The Minnesota Colon Cancer Control Study showed that annual FOBT screening  reduced colorectal cancer mortality by about 3 deaths per 1000 people screened after 13 years of follow up9 . Similarly , screening  reduced the risk for cancer diagnosis by just 7 per 1,000 people screened after 18 years of follow up10 . This small likelihood of future benefit must then be weighed against the more immediate potential downsides of screening , including false positive tests , the costs and risks of invasive diagnostic tests , treatment complications , and the risk for overdiagnosing cancer — finding disease that is not destined to cause any problems during a patient′s lifetime . The latter problem is particularly pertinent for cancer screening in sick and elderly patients . To minimize inappropriate and potentially harmful screening , the US Preventive Services Task Force has recently provided explicit guidelines —no screening after age 85 and personalized screening decisions for those ages 76 to 8511 . These recommendations are partly based on the trial data showing that colorectal cancer survival curves did not diverge until 5 years after the start of screening . This interval reflects that it often takes many years between when a cancer could be first detectable by screening until when it would have grown large enough to cause symptoms or death . The recommendation for “ personalized ” screening decisions really is a call for informed decision making . Older patients , especially those who have serious medical illnesses , need to be aware that they are least likely to live long enough to receive any benefit from cancer screening and more likely to experience the complications from tests and treatments . The study by Kahi and colleagues did not address whether physicians would elicit patient preferences or support informed decision-making , but the fact that respondents reported that they would offer screening to patients over age 85 or to 75-year-old patients with cancers or severe heart failure is disconcerting . These patients clearly are very unlikely to derive any benefit from screening and are at substantial risk for being harmed . While these are survey data and respondents were presented with hypothetical scenarios , it appears that actual screening practice s may indeed be quite inappropriate . A recent cohort study of older veterans at four VA medical centers used linked VA and Medicare data to describe screening practice s12 . During calendar years 2001 and 2002 , 37.6 % of veterans aged 80 and older who were due for colorectal cancer screening underwent screening with FOBT , endoscopy , or barium enema . Strikingly , among this group , the screening rate was 34 % for those with severe comorbidity ( defined by Charlson – Deyo scores ≥ 4 ) , only slightly lower than the 38 % screening rate for those who had comorbidity scores of 0 . Why is this happening ? Several authors have suggested that organizational zeal to boost screening rates by converting practice guidelines into performance measures can increase the rate of inappropriate screening in the sick and elderly13,14 . Similarly , public service messages targeting the public may oversimplify the screening message—“just do it”—rather than presenting accurate , balanced information about the pros and cons of screening . Such oversimplified messages likely contribute to why many patients do not make informed decisions about cancer screening and why frail elderly patients continue to undergo cancer screening , even when the risks are substantial and the benefits are remote . What can be done about this ? Clearly , organizations need to more carefully balance performance measures and financial incentives with evidence -based guidelines . Quality -of-care assessment s must identify and reward efforts that target patients most likely to benefit from screening rather than those efforts that merely increase screening rates . Optimizing the targeting of cancer screening also may require changes in how preventive care is delivered . The current system for delivering preventive care relies on finding opportunities for screening when patients see clinicians for medical problems , which targets screening to elderly patients with more serious comorbid conditions because they see clinicians more frequently . This system misses healthy patients who see clinicians less frequently . In addition , both patients and clinicians need to be more aware of the potential risks associated with screening , especially for persons with advanced age and serious comorbidities . When two out of three outcomes for the forward pass are bad , the coach and players need to carefully study the playbook and make an informed decision This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer . The study included 2962 patients with breast , lung , colorectal , lymphoma , and ovarian cancers from a prospect i ve U.S. registry of patients initiating a new chemotherapy regimen .  Detailed patient- , disease- , and treatment-related data , including toxicities , were captured at baseline , the beginning of each cycle , and each midcycle blood draw for up to 4 cycles of treatment . Primary outcomes included febrile neutropenia ( FN ) , severe neutropenia without fever/ infection , and relative dose intensity ( RDI ) .  Thirty-seven percent of patients were aged 65 years or older , 43.5 % had an Eastern Cooperative Oncology Group performance status of 1 or greater , and 27 % had 1 or more comorbidities . Reductions in RDI to less than 85 % of st and ard in the first cycle were planned in 23.6 % of patients , whereas primary colony-stimulating factor prophylaxis was used in 18.2 % . In the first 3 cycles of treatment , 10.7 % of patients experienced FN , with most of these events ( 58.9 % ) occurring in the first cycle . This first-cycle pattern was consistently observed despite wide variations in event rates by tumor type , disease stage , chemotherapy regimen and dose , and patient characteristics . Despite frequent planned reductions from st and ard RDI , the incidence of FN remains high in community oncology practice in the United States . Improved methods of pretreatment assessment of patient risk factors for neutropenia are needed Neutropenic complications remain an important dose‐limiting toxicity of cancer chemotherapy‐associated with considerable morbidity , mortality , and cost . Risk of the initial neutropenic event is greatest during the first cycle . The purpose of this study was to better underst and timing of neutropenic events in relation to delivered chemotherapy dose intensity and utilization of supportive care during cancer treatment . A prospect i ve cohort study of adult patients with solid tumors or lymphoma initiating chemotherapy was conducted at 115 r and omly selected US practice sites between 2002 and 2006 .  Chemotherapy‐associated toxicities were captured in up to four treatment cycles including severe neutropenia , febrile neutropenia , and infection . Documented interventions included colony‐stimulating factor ( CSF ) , antibiotics use , and reductions in chemotherapy relative dose intensity ( RDI ) . A total of 3638 patients with breast ( 39.7 % ) , lung ( 23.7 % ) , colorectal ( 13.6 % ) , ovarian ( 8.3 % ) cancers , or lymphoma ( 14.7 % ) were eligible for this analysis . The majority of neutropenic and infection events occurred in the first cycle . A significant inverse relationship was observed between reductions in neutropenic and infectious events and increased utilization of measures to reduce these complications in subsequent cycles . More than 60 % of patients with stage IV solid tumors underwent reductions in RDI . Patients with lymphoma and stage I – III solid tumors had less dose reductions while receiving more prophylactic CSFs . Approximately , 15 % of patients received prophylactic antibiotics . While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy , subsequently instituted clinical measures in efforts to reduce the risk of these events vary with cancer type and stage BACKGROUND This study was conducted to analyze the feasibility of adjuvant capecitabine therapy using a tailored-dose escalation strategy in elderly patients with colon cancer ( CC ) . METHODS CC patients ( ≥ 70 years of age ) who received adjuvant capecitabine were enrolled . The starting dosage of capecitabine was 2000 mg/m(2)/day ( days 1 - 14 , every 3 weeks ) . On the second cycle , the dosage was escalated to 2500 mg/m(2)/day if the patient tolerated the first cycle . Dose intensity ( DI ) , toxicity , and the change in quality of life ( QoL ) were evaluated . RESULTS Of 82 patients enrolled , 67 completed eight cycles . Dose escalation to 2500 mg/m(2)/day was possible in 56 patients , and this dosage was maintained in 24 patients until the completion of chemotherapy ( eight cycles ) . Forty-one patients completed therapy with a DI ≥ 1333 mg/m(2)/day [ relative dose intensity ( RDI ) ≥ 80 % ] . Toxic effects were tolerable and the QoL was not compromised during treatment . Creatinine clearance < 50 ml/min and Charlson-Age comorbidity index ≥ 8 were related to a reduced capecitabine dosage ( RDI < 80 % ) . CONCLUSIONS A tailored-dose escalation strategy was feasible in elderly CC patients receiving adjuvant capecitabine chemotherapy .  Decreased renal function and an increased number of comorbidities were independently predictive of reduced administration of the capecitabine dose A phase II double-blind placebo-controlled , r and omized dose-ranging trial was undertaken to determine the antiemetic efficacy and toxicity of the synthetic cannabinoid levonantradol at doses of 0.5 , 1.0 , 1.5 , and 2.0 mg . Intramuscular levonantradol was prophylactically administered in r and om dosing to 20 subjects with a documented history of refractory emesis due to chemotherapy in advanced cancer . The selected dose was administered prior to the chemotherapy and was serially repeated over 12 hours , and efficacy and toxicity data were evaluated for 24 hours . Significant ( P less than 0.01 ) antiemetic activity over placebo was observed with all doses of levonantradol administered , and a dose-effect response was not observed . Doses up to 2.0 mg were well tolerated , and observed toxicity increased with increased doses and with repeated dosing . Psychomimetic effects were mild and tolerable , and the limiting side effects were somnolence and hypotension BACKGROUND Older patients , even if fit , are often considered incapable of tolerating platinum-based systemic therapy . We performed a retrospective analysis of Eastern Cooperative Oncology Group ( ECOG ) 5592 , a phase III r and omized trial of platinum-based chemotherapy regimens for non-small-cell lung cancer ( NSCLC ) , and compared outcomes in enrollees 70 years of age and older with those in younger patients . METHODS ECOG carried out a r and omized phase III trial of cisplatin plus either etoposide or paclitaxel in chemotherapy-naïve NSCLC patients with stages III(B ) or IV disease .  Toxic effects , response rates , and survival rates were compared between age groups . All P values were two-sided . RESULTS A total of 574 patients enrolled from August 1993 through December 1994 were evaluable . Eighty-six ( 15 % ) were 70 years old or older . Older patients had a higher incidence of cardiovascular ( P = .009 ) and respiratory ( P = .04 ) comorbidities and nonanalgesic medication use ( P = .02 ) . Leukopenia ( P<.001 ) and neuropsychiatric toxicity ( P = .002 ) were more common in elderly men than in younger men . Elderly women lost more weight than younger women ( P = .006 ) . Other toxic effects were similar in older and younger patients . The proportions with clinical partial or complete response ( 21.5 % versus 23.3 % ; Fisher 's exact test , P = .66 ) , median time to progression ( 4.37 versus 4.30 months ; log-rank test , P = .29 ) , and survival distribution ( log-rank test , P = .29 ; median survival , 9.05 versus 8.53 months ; 1-year survival , 38 % versus 29 % ; and 2-year survival , 14 % versus 12 % ) were similar in patients younger than 70 years and 70 years old or older . Baseline quality -of-life and treatment- outcome indices were similar . Equivalent declines over time in functional well-being occurred in both groups . CONCLUSION Response rate , toxicity , and survival in fit , elderly NSCLC patients receiving platinum-based treatment appear to be similar to those in younger patients , although patients 70 years old or older have more comorbidities and can expect more leukopenia and neuropsychiatric toxicity . Advanced age alone should not preclude appropriate NSCLC treatment Background Elderly patients with metastatic breast cancer ( MBC ) have more problems receiving chemotherapy than younger patients , especially with the presence of multiple comorbidities , adverse drug events and functional decline . Low-dose oral administration of cytotoxic agents such as vinorelbine , a semisynthetic vinca alkaloid that interferes with microtubule assembly , leading to arrest of cell division , is usually effective and well tolerated . Methods From February 2010 to February 2014 , 32 patients with MBC , median age 76 years ( range 69 - 83 ) were treated with oral vinorelbine 30 mg ( total dose ) , one day on and one day off , until disease progression or unacceptable toxicity levels were reported . Toxicity , quality of life and clinical benefit were evaluated . Matched t-tests were conducted to discern whether quality -of-life indicator ( p<0.05 was considered significant ) differed before and 6 months after treatment . Statistical analysis was performed using Graph Pad Prism 5.0 ( GraphPad Software Inc. , San Diego , CA , USA ) . Results No grade 3 and 4 adverse events were reported . A clinical benefit of 50 % was found in our cohort . On and off metronomic vinorelbine oral administration result ed in good tolerability and safe profile in our selected elderly population , and improved patient adherence to therapy . Conclusions The present study demonstrated that metronomic vinorelbine might be a potential treatment in elderly patients by reducing adverse effects and increasing quality of life , setting the stage for future extensive clinical trials We present experience from a phase II r and omized clinical trial , comparing st and ard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer ( NSCLC ) and who are unfit for st and ard platin-based chemotherapy . Eligible patients had microscopically confirmed NSCLC in stage IIIB ( wet ) or IV , were chemo-naive , and were in poor performance status or presented with significant comorbidity .  St and ard treatment with gemcitabine , 1250 mg/m2 in 20–30 min on days 1 and 8 as monotherapy ( arm A ) was compared with low-dose gemcitabine in long infusion ( 200 mg/m2 in 6 h on day 1 ) and cisplatin at 60 mg/m2 on day 2 ( arm B ) . Both treatment schedules were repeated every 3 weeks until disease progression , unacceptable toxicity , or to a maximum of six cycles . A total of 112 patients ( 83 male , 29 female , median age 66 years ) were r and omized between arm A ( 57 patients ) and B ( 55 patients ) . The two groups were balanced for prognostic factors . Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response . The median number of cycles was four and five for arms A and B , respectively . Except for grade 3 anemia ( one patient in arm A and two in arm B ) , no other major toxicity was seen . Regarding response to treatment , arm B was superior : 1 complete response and 13 partial remissions ( response rate 26.9 % ) as compared with five partial remissions ( response rate 9.4 % ) in arm A ( P<0.01 ) . The median time to progression was 3.8 and 5.6 months , and the median survival was 4.3 and 6.8 months for arms A and B , respectively ( P<0.05 ) . Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity , is effective , was found to be superior to monotherapy with gemcitabine in st and ard doses , and is suitable for patients with NSCLC who can not tolerate a st and ard platin-based doublet Purpose Lung cancer chemotherapy decisions in patients ≥70 years old are complex because of toxicity , comorbidity and the limited data on patient preferences . We examined the relationships between preferences and chemotherapy use in this group of patients . Methods and patients We used a question naire describing four hypothetical lung cancer treatment options .  Eighty-three elderly ( ≥70 years old ) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options . Patients had previously been included in a prospect i ve study to explore geriatric evaluation in an oncology unit and all had given written informed consent . Results Older patients ( n=83 ) diagnosed with lung cancer ( non-small- and small-cell lung cancer ) from January 2006 to February 2008 were recruited from a single centre . The mean patient age was 77 years ( range : 70–91 ) . Eighty-one patients ( 97.6 % ) were men . Non-small-cell lung cancer ( NSCLC ) was the diagnosis in 63 patients ( 76 % ) . Most patients selected active treatment ( 38.6 % most survival benefit , 18 % less survival benefit ) and 31.3 % selected no active treatment . Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities . Although most of the patients were symptomatic at diagnosis , the “ symptom relief ” option was chosen less frequently than the options that could prolong survival . Factors significantly related to patients ’ attitude toward chemotherapy were age ( p<0.001 ) , frailty ( p=0.0039 ) , depression and poor performance status ( PS ) . Conclusion Elderly lung cancer patients want to be involved in the decision-making process . Survival was the main treatment objective for more than half of the patients in this study . We have not found other published studies about elderly lung cancer patients ’ decisions about chemotherapy CONTEXT Patients with cancer often have other medical ailments , referred to as comorbidity . Comorbidity may impact treatment decision-making , prognosis , and quality of care assessment . OBJECTIVE To assess whether comorbidity information can provide important prognostic information in a hospital-based cancer registry . DESIGN , SETTING , AND PARTICIPANTS An observational prospect i ve cohort study using comorbidity data collected by trained hospital-based cancer registrars . Comorbidity was obtained through medical record review using the Adult Comorbidity Evaluation 27 , a vali date d chart-based comorbidity instrument . A total of 17,712 patients receiving care between January 1 , 1995 , and January 31 , 2001 , for the primary diagnosis of new cancer of the prostate , lung ( nonsmall cell ) , breast , digestive system , gynecological , urinary system , or head and neck were included . MAIN OUTCOME MEASURE Duration in months of overall survival . RESULTS A total of 19,268 patients were included in the study ; median duration of follow-up was 31 months . Of these patients , 1556 ( 8.0 % ) were excluded due to missing or unknown data . Severity of comorbidity strongly influenced survival in a dose-dependent fashion and the impact of comorbidity was independent of cancer stage . Compared with patients without comorbidity , the adjusted hazard ratio associated with mild comorbidity was 1.21 ( 95 % confidence interval [ CI ] , 1.13 - 1.30 ) , moderate comorbidity was 1.86 ( 95 % CI , 1.73 - 2.00 ) , and severe comorbidity was 2.56 ( 95 % CI , 2.35 - 2.81 ) . Adjusted Kaplan-Meier survival curves revealed that at any point in time the patients with more severe levels of comorbidity had worse survival ( partial chi2(3 ) due to comorbidity , 523.54 ; P<.001 ) . Model discrimination ranged from 0.71 for head and neck to 0.86 for prostate cancers . CONCLUSIONS Comorbidity is an important independent prognostic factor for patients with cancer . The inclusion of comorbidity in hospital-based cancer registries will increase the value and use of observational research Breast cancer is the second most common type of cancer among women in the United States with more than 200,000 women diagnosed with invasive disease and with approximately 40,000 dying annually from the disease ( 1 ) . As a result of early detection efforts , nearly half of these women present with lymph node negative hormone receptor positive disease . Current treatment for early-stage breast cancer ( ESBC ) with adjuvant hormonal therapy and /or chemotherapy is based on clinical and pathological criteria including the presence and number of involved lymph nodes , tumor size and grade , hormone receptor status , and the presence of HER2/neu overexpression among others . Treatment decisions may also take into consideration patient age or menopausal status due to the anticipated lower risk of cancer recurrence , and the potential for smaller benefit and greater toxicity with aggressive systemic chemotherapy in older women . These considerations form the basis for clinical practice guidelines for the management of patients with ESBC ( 2 , 3 ) . Current guidelines recommend adjuvant systemic chemotherapy and endocrine therapy for most women with lymph node negative , hormone receptor positive , ESBC . Unfortunately , such systemic chemotherapy is associated with considerable cost , proximal morbidity , as well as increasing evidence for serious delayed toxicities including neurocognitive dysfunction and secondary malignancies . The risk of distant recurrence is generally low among ESBC patients with lymph node negative , hormone receptor positive disease regardless of treatment with adjuvant chemotherapy . However , several r and omized controlled trials of adjuvant chemotherapy and meta-analyses have shown the value of adjuvant chemotherapy in reducing the risk of disease Purpose To increase awareness , outline strategies , and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor ( ICPi ) therapy .  Methods A multidisciplinary , multi-organizational panel of experts in medical oncology , dermatology , gastroenterology , rheumatology , pulmonology , endocrinology , urology , neurology , hematology , emergency medicine , nursing , trialist , and advocacy was convened to develop the clinical practice guideline . Guideline development involved a systematic review of the literature and an informal consensus process . The systematic review focused on guidelines , systematic review s and meta-analyses , r and omized controlled trials , and case series published from 2000 through 2017 . Results The systematic review identified 204 eligible publications . Much of the evidence consisted of systematic review s of observational data , consensus guidelines , case series , and case reports . Due to the paucity of high- quality evidence on management of immune-related adverse events , recommendations are based on expert consensus . Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented . While management varies according to organ system affected , in general , ICPi therapy should be continued with close monitoring for grade 1 toxicities , with the exception of some neurologic , hematologic , and cardiac toxicities .  ICPi therapy may be suspended for most grade 2 toxicities , with consideration of resuming when symptoms revert to grade 1 or less . Corticosteroids may be administered . Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids ( prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d ) . Corticosteroids should be tapered over the course of at least 4 to 6 weeks . Some refractory cases may require infliximab or other immunosuppressive therapy . In general , permanent discontinuation of ICPis is recommended with grade 4 toxicities , with the exception of endocrinopathies that have been controlled by hormone replacement . Additional information is available at www.asco.org/supportive-care- guidelines and www.asco.org/ guidelines wiki Abstract Purpose Multimodal therapies affect the quality of life ( QoL ) of patients with primary breast cancer ( PBC ) . The objectives of this prospect i ve study were to explore the changes in QoL from diagnosis to conclusion of adjuvant therapy and to identify predictive factors of QoL. Methods Before surgery ( t1 ) , before onset of adjuvant treatment ( t2 ) and after completion of adjuvant chemo- or radiotherapy ( t3 ) , patients with PBC ( n = 759 ) completed the European Organization for Research and Treatment of Cancer Quality of Life Core Question naire , Charlson Comorbidity Index , Patient Health Question naire and Perceived Involvement in Care Scales . Predictors of the course of global QoL were estimated using multinomial logistic regression . Effect estimates are odds ratios ( OR ) and their 95 % confidence intervals ( CIs ) . Results Global QoL improved between t1 and t3 , while physical functioning , emotional functioning and fatigue deteriorated . QoL before surgery was more often poor in patients < 60 years ( OR 2.2 , 95 % CI 1.5–3.1 ) and in those with comorbid mental illnesses ( OR 8.6 , CI 5.4–13.7 ) . Forty-seven percentage reported good global QoL both at t1 and at t3 . QoL improved in 28 % , worsened in 10 % and remained poor in 15 % . Compared to patients with consistently good global QoL , a course of improving QoL was more often seen in patients who had received a mastectomy and in those with intense fear of treatment before surgery . A course of decreasing QoL was more often found in patients who were treated with chemotherapy . QoL stayed poor in patients with chemotherapy , mastectomy and intense fear . There was no evidence that radiotherapy , progressive disease or perceived involvement impact the course of QoL. Conclusions Younger age and comorbid mental illnesses are associated with poor QoL pre-therapeutically . QoL is more likely to stay or become poor in patients who receive chemotherapy The benefits established in efficacy trials , usually r and omized , controlled trials conducted under highly controlled circumstances with maximized internal validity , can frequently not be demonstrated in clinical practice at the community level . Effectiveness trials are tools to evaluate the applicability of a treatment in a wider setting with maximized external validity , to observe uncommon adverse events , and to identify factors influencing the main outcomes and risks . Important areas in relation to lung cancer treatment that will benefit from effectiveness trials include gefitinib monotherapy and bevacizumab therapy combined with cytotoxic chemotherapy for advanced non-small cell lung cancer . These therapies were found to produce life-threatening nonhematologic toxicity at a high incidence of up to 5 % ; however , the risk factors for these toxicities have not yet been fully established . Effectiveness trials of adjuvant chemotherapy after surgery with long-term follow-up are also important to obtain reliable information as to secondary malignancy and noncancer-related deaths . Development of an infrastructure for effectiveness trials is crucial because of the necessity to deal with large numbers of patients , sometimes as many as 10,000 patients , from many hospitals . The extensive research time involved and the considerable cost of these trials may be reduced with the use of Internet re sources . Effectiveness trials are a fundamental step toward bridging the gap between clinical research and clinical practice and effectively implementing new therapies in clinical practice PURPOSE The goal of the computer program Adjuvant ! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy . METHODS Actuarial analysis was used to project outcomes of patients with and without  adjuvant therapy  based on estimates of prognosis largely derived from Surveillance , Epidemiology , and End- Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of r and omized trials of adjuvant therapy . These estimates can be refined using the Prognostic Factor Impact Calculator , which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results . RESULTS From the entries of patient information ( age , menopausal status , comorbidity estimate ) and tumor staging and characteristics ( tumor size , number of positive axillary nodes , estrogen receptor status ) , baseline prognostic estimates are made . Estimates for the efficacy of endocrine therapy ( 5 years of tamoxifen ) and of polychemotherapy ( cyclophosphamide/methotrexate/fluorouracil-like regimens , or anthracycline-based therapy , or therapy based on both an anthracycline and a taxane ) can then be used to project outcomes presented in both numerical and graphical formats . Outcomes for overall survival and disease-free survival and the improvement seen in clinical trials , are reasonably modeled by Adjuvant ! , although an ideal validation for all patient subsets with all treatment options is not possible . Additional speculative estimates of years of remaining life expectancy and long-term survival curves can also be produced . Help files supply general information about breast cancer . The program 's Internet links supply national treatment guidelines , cooperative group trial options , and other related information . CONCLUSION The computer program Adjuvant ! can play practical and educational roles in clinical setting
This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice , due to the careful selection of patients with fewer comorbidities .
Although guidelines exist for the estimation of chemotherapy dose , clinical factors like age , comorbid illness and extremes of body habitus are not considered in the method of dose calculation , which can result in significant toxicity .