Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first‑line chemotherapy from a tertiary cancer center in India.

INTRODUCTION: Unlike the developed countries, there is a lack of good epidemiologic data for testicular germ cell tumors (GCTs) in India with majority presenting in advanced stage. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard first‑line chemotherapy (CT). METHODS: GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (bleomycin, etoposide, and cisplatin/etoposide and cisplatin/carboplatin AUC7) and radiotherapy were given as appropriate. Response was calculated based on the Response Evaluation Criteria in Solid Tumors. Statistical analysis was performed using SPSS 18 software. RESULTS: Fifty nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5–19) in NSGCT and 5.5 cm (1.3–11) in SGCT. As per the International Germ Cell Cancer Collaborative Group classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia, Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. CONCLUSIONS: GCTs in India present with high nodal and high‑risk diseases wherein the standard first‑line CT may not be adequate as curative therapy; however, significant chemotoxicity is also a hindrance.

Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage.

OBJECTIVES: To study the utility of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting (1) the World Health Organization (WHO) histologic type and differentiating low‑risk from high‑risk types. (2) Tumor stage and differentiate early from advanced stage disease. MATERIALS AND METHODS: Patients with thymic epithelial neoplasia who underwent a pretreatment FDG‑PET study were included. Tumor maximum standardized uptake value (SUVmax) was correlated with the WHO histologic type and also with the Masaoka‑Koga (MK) staging system. Patients with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas belonged to Type C. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage. Differences in SUVmax between the various groups were calculated. RESULTS: The SUVmax of thymic carcinomas was significantly higher as compared to low‑risk (P = 0.001) and high‑risk groups (P = 0.007). The SUVmax of high‑risk group was also significantly higher than the low‑risk group (P = 0.002). SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with 100% sensitivity and 87.2% specificity. The SUVmax in patients with advanced stage disease showed a higher trend compared to those with early stage, but the difference was not significant (P = 0.167). CONCLUSION: PET can differentiate thymic carcinomas from rest of the thymoma subtypes by the virtue of their higher FDG uptake. It can also provide valuable information in differentiating high‑risk from low‑risk thymomas and in predicting disease stage.

Current evidence and the evolving role of sunitinib in the management of renal cell carcinoma.

The development of targeted agents has expanded the anticancer arsenal available to oncologists and revolutionized the field of cancer treatment. In patients with advanced renal cell carcinoma (RCC), small molecule targeted therapies have improved clinical outcomes compared with cytokine‑based treatments. Sunitinib malate is one such drug that has demonstrated clinical efficacy in patients with metastatic renal cell carcinoma (mRCC). This oral, multi‑targeted tyrosine kinase inhibitor is approved for use in multiple countries for the treatment of advanced RCC and gastrointestinal stromal tumor patients who have progressed on imatinib therapy. In patients with advanced RCC, sunitinib significantly improves clinical outcomes with a favorable safety profile compared with conventional treatment with interferon‑a. The clinically proven treatment and safety outcomes have led investigators to evaluate the merits of sunitinib therapy in the adjuvant and neoadjuvant setting in patients with mRCC. In the neoadjuvant setting, preliminary data suggest that sunitinib can effectively reduce the primary tumor and facilitate surgical resection in patients with locally advanced and mRCC. Post‑operative complications were observed in some patients, but the overall safety profile and efficacy suggests that mRCC patients with surgically inoperable tumors may benefit from neoadjuvant sunitinib therapy. Ongoing clinical trials should provide insight into the value of sunitinib as adjuvant therapy.

Optimizing treatment and analysis of prognostic factors for locally advanced nonsmall cell lung cancer in resource‑limited population.

BACKGROUND: Lung cancer most commonly presents in advanced stages in developing countries, where combined modality treatment using chemo‑radiotherapy (CTRT) is the standard of care. MATERIALS AND METHODS: A retrospective audit of patients of nonsmall cell lung cancer (NSCLC) treated at a single Institute from January 2008 to December 2012 was conducted. Various prognostic factors affecting disease‑free survival (DFS) and overall survival (OS) were studied by univariate and multivariate analysis. All patients were meticulously followed‑up clinically and telephonic contacts. RESULTS: Overall 171 patients of NSCLC were treated with definitive CTRT using concurrent chemotherapy in 66% patients and sequential therapy in 28% patients. The actuarial 2 years DFS was 17.5% and 2 years OS was 61.5%. Complete response to treatment resulted in significantly better DFS and OS. Definitive CTRT was very well‑tolerated in these patients with good compliance. CONCLUSION: Definitive CTRT, sequence being individualized depending on performance status and disease stage at presentation, is a feasible and effective treatment modality for locally advanced NSCLC patients in the developing world. Response to treatment is an important prognostic factor for treatment outcomes.

Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non‑small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro‑intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular‑guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient’s quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment. These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient’s quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non‑Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

Efficacy of second‑line erlotinib in patients postprogression of first‑line chemotherapy in head and neck cancers.

BACKGROUND: Oral tyrosine kinase inhibitor (gefitinib and erlotinib) have been used in the palliative treatment of head and neck cancers with limited success. In this report, we aim to quantify the symptomatic benefit, progression‑free survival (PFS) and overall survival (OS) when erlotinib is given as second‑line treatment in Head and neck cancers. METHODS: This was a post‑hoc retrospective analysis of a randomized study comparing metronomic chemotherapy with cisplatin. A patient who progressed on chemotherapy and had a PS0‑2 were offered second‑line chemotherapy. Patients who had received erlotinib (150 mg PO OD) as second line treatment were selected for this analysis. Erlotinib was discontinued in case of either progression of disease or if the patient had intolerable side effects. Patient were monitored 1‑week after the start of erlotinib and subsequently at monthly intervals. The toxicity was recorded in accordance with CTCAE version 4.02 (NCI,USA) and the response were graded in accordance with RECIST version 1.1. All of these patients were followed‑up till death. RESULTS: Twenty‑three patients were identified. The median age of these patients at the start of the second line was 47 years (interquartile range 40.5–51.75 years). The primary site of distribution was oral cavity primary in 17 patients (77.3%) and nonoral cavity primary in 05 (22.7%) patients. The immediate last chemotherapy regimen received was cisplatin in 9 patients (40.9%) and metronomic chemotherapy in 13 patients (59.1%). Symptomatic benefits post second‑line erlotinib was seen in 18 patients (81.8%). The most common adverse events (any grade) seen were anemia in 20 patients (90.9%), rash in 10 patients (45.5%) and diarrhea in 7 patients (31.8%).The best radiological response documented were a partial response in 04 patients (19.2%). The median estimated PFS and OS were 110 days (95% confidence interval [CI]: 61–175 days) and 156 days (95% CI: 126–185 days) respectively. CONCLUSION: Erlotinib single agent has promising activity in the second line and needs to be explored in future studies.

Predictivity of human papillomavirus positivity in advanced oral cancer.

BACKGROUND AND OBJECTIVE: Human papillomavirus (HPV) is a known prognostic factor world over in patients of carcinoma oropharynx. The role of HPV in oral cancers has not been investigated adequately. We tried to identify standard clinicopathological features in oral cancer, which would predict HPV‑positivity. METHODS: This was a retrospective analysis of 124 cases of T4 oral cancer patients at our center. HPV‑positive was defined in accordance with positive p16 immunohistochemistry done on pretreatment local tumor site biopsy. Age, sex, habits (smoking history and oral tobacco), Eastern Cooperative Oncology Group performance status (ECOG PS), T stage, N stage, grade, and site were selected, for testing of prediction for HPV‑positivity. The analysis was performed by R studio version 3.1.1. Two‑sample test for equality of proportions with continuity correction was used to identify factors predicting for HPV‑positivity. P = 0.05 was considered as significant. RESULTS: Of 124 patients, 16 patients (12.9%) were HPV‑positive. The median age of the whole cohort was 43 years (interquartile range 37–52 years) with 15 females (12.1%). All had squamous cell carcinoma (100%). The grade of the tumor was well differentiated in 9 patients (7.2%), moderately differentiated in 98 patients (79.1%), and poorly differentiated in 17 patients (13.7%). The ECOG PS 0 in 19 patients (15.3%), 1 in 104 patients (83.9%), and 2 in 1 patient (0.8%). The subsite of the tumor was buccal mucosa in 74 patients (59.7%), anterior two‑third of tongue in 33 patients (26.6%), and others in 17 patients (13.7%). None of the tested factors except the use of oral tobacco were statistically significantly associated with HPV‑positivity. History of tobacco usage had a statistical trend toward ability to predict HPV‑positivity. The proportion of patients with HPV‑positive oral cancer in patients without history usage of oral tobacco was 31.3% while it was 10.2% in patients with previous history of tobacco use (P = 0.03). CONCLUSION: Standard clinicopathological variables could not predict for HPV‑positivity. Negative history of tobacco (smokeless) usage showed statistical trends toward ability to predict HPV‑positivity in oral cancer patients.

Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers.

BACKGROUND: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. METHODS: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow‑up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi‑square analysis was done to compare response rates (RRs) between regimens. RESULTS: Two hundred and forty‑five patients were identified. The median age was 45 years (24–70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). CONCLUSIONS: TPF has better RR than a 2 drugs taxane‑containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.

Management of febrile neutropenia in malignancy using the MASCC score and other factors: Feasibility and safety in routine clinical practice.

BACKGROUND: The current standards for empirical broad‑spectrum intravenous antibiotic (AB) treatment, combined with hospitalization, are cautious and safe, but lead to over‑treatment of a substantial group of patients. We need to validate parameters to identify these low‑risk febrile‑neutropenia (FN) patients, who could then be safely treated in an outpatient setting with minimal/no AB treatment. MATERIALS AND METHODS: A retrospective analysis for validation of a risk‑assessment model in FN patients was done on a patient population from January 2007 to December 2008. Inclusion criteria were a histological diagnosis of malignancy, FN secondary to chemotherapy, absolute‑neutrophil‑count of ≤500/μl, axillary temperature of ≥38°C, and age ≥14 years. Other clinical and laboratory parameters were explored for risk stratification during the FN episodes. Receiver‑operating characteristic curves were used to find the threshold value, and Chi‑square analysis was done to find the association between the outcome and the parameters. RESULTS: A total of 178 FN episodes were documented; 22 in solid tumors and 156 in hematolymphoid malignancies. Culture positivity was documented in 59 episodes; peripheral blood was the most common source, with Escherichia coli being the most common organism identified. Risk stratification was done using the Multinational Association of Supportive Care in Cancer (MASCC) risk‑index score. The association between the MASCC score and risk stratification could not be established (P = not significant) at a score of ≤21; however, it was found to be significant at a score of ≤18. The total number of complications was 23 (sepsis 22, mortality 23). Other factors found to be significantly associated with a high risk of complications in the univariate analysis were, mucositis (P = 0.03), maximum temperature ≥103°F (P = 0.01), tachycardia (P < 0.001), tachypnea (P = <0.001), age (P = 0.006), high dose of steroid (P < 0.001), total duration of fever (≥2.5 days (for which sensitivity (S) and specificity (Sp) were 87 and 81%, respectively), serum‑creatinine (≥0.45 mg%, S = 100%, Sp = 97%), serum‑bilirubin (≥0.5 mg/dl, S = 100%. Sp = 90%), requirement of second‑line antibiotics (P = 0.02), intensive‑care (P ≤ 0.001), ventilatory support (P < 0.001), and requirement of packed cell (PC) transfusion (P = 0.02). In the multivariate analysis, mucositis (P = 0.02), HD steroid use (P = 0.026), and PC requirement (0.026) were identified as independent variables. CONCLUSIONS: The MASCC risk‑index score was found to be meaningful at a score of ≤18. Other clinical and laboratory parameters were found to have a strong association with risk stratification in cancer patients during FN episodes.

Pattern of infection, therapy, outcome and risk stratification of patients with febrile neutropenia in a tertiary care oncology hospital in India.

CONTEXT: Indian febrile neutropenia (FN) data are limited, especially in adult solid tumor patients. AIMS: The aim was to study patterns of presentation, source of infection, management and outcome and to evaluate the factors which may correlate with outcome. MATERIALS AND METHODS: A retrospective analysis of prospective data of FN patients at a tertiary care oncology teaching hospital in India between 2007 and 2012. A standardized form was filled for each patient. Patient management was at the discretion of the treating physician. Multinational Association for Supportive Care in Cancer (MASCC) score was retrospectively calculated. Failure of therapy was defined as death, organ failure, shifting from outpatient to inpatient or requirement of intensive care support. SPSS version 16 was used for analysis. RESULTS: A total of 388 FN episodes were included: 256 in hematolymphoid and 132 in solid tumor patients. 156 episodes were high‑risk by MASCC score. Focus of infection was clinical in 45% and radiologic in 16%. Blood cultures were positive in 18% cases, most commonly Gram‑negative organisms (72%). 93% patients were treated with an antibiotic combination of third‑generation cephalosporin/beta‑lactamase inhibitor, with aminoglycoside or fluoroquinolone. Antibiotic sensitivity to ceftriaxone was low at 38% while sensitivity to cefoperazone/sulbactam and piperacillin/tazobactam ranged between 50% and 55% and for carbapenems 75%. Failure of therapy occurred in 156 episodes, most commonly due to the need for second line antibiotics. Mortality was 5.5%. On univariate analysis, MASCC score, age, type of malignancy, prophylactic growth factors, presence of focus of infection, hemoglobin and nadir platelet count correlated with FN complications. CONCLUSION: Gram‑negative bacteremia continues to be the predominant cause of FN in our setup.

Leptomeningeal metastasis in solid tumors with a special focus on lung cancer.

Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer.

Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer.

Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2), progression (1) and logistics (1). Two of the three patients with measurable disease attained a partial remission (PR). Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN), all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.