LinuAbraham Jacob

Current status of systemic therapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck

Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab. Epidermal growth factor receptor inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only a modest success in R/M HNSCC. Immunotherapy represents an attractive treatment option for R/M HNSCC, with encouraging preliminary data from studies involving immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) and toll-like receptor agonists (e.g., motolimod). Given the poor prognosis of R/M HNSCC, enrollment of patients into clinical trials to investigate novel systemic agents, is necessary for further improvement of oncologic outcomes in this patient population.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience

Background: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. Methods: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. Results: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318–0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. Conclusion: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.

Cancer of unknown primary: Opportunities and challenges

Cancer of unknown primary (CUP) is defined as histologically proven metastatic tumors whose primary site cannot be identified during pretreatment evaluation. Among all malignancies, 3%–5% remained as CUP even after the extensive radiological and pathological workup. Immunohistochemistry and molecular gene expression tumor profiling are being utilized to predict the tissue of origin. Unfortunately, the survival of these patients remains poor (6–9 months) except in 20% of patients who belong to a favorable subset (12–36 months). There is a need to understand the basic biology and to identify the molecular pathways which can be targeted with small molecules. This article reviews our current approach as well as treatment evolution occurred in the past three decades.

Clinicopathological profile and treatment outcomes of bilateral breast cancer: A study from tertiary cancer center in South India

Background: Bilateral breast cancer (BBC) is a rare clinical entity with limited data regarding clinicopathological aspects and treatment guidelines. Materials and Methods: This was an observational study of patients diagnosed with BBC from August 2012 to July 2014. Synchronous breast cancers (SBCs) was defined as two tumors diagnosed within an interval of 6 months and metachronous breast cancer (MBC) as second cancer diagnosed after 6 months. Results: Out of 750 breast cancer patients seen during a 2-year period, 35 had BBC. Ten patients were diagnosed as SBC whereas 25 patients as MBC. Among patients with MBC, the average time for development of contralateral breast cancer was 5 years. In 8 patients, the contralateral breast cancer was detected mammography whereas rest 27 patients were detected by clinical breast examination. At a median follow-up of 24 months, 23 (66%) patients were disease free, 9 (26%) patients had disease relapse, and 3 (8%) patients succumbed to the progressive disease. Conclusions: Every patient with breast cancer should be regularly followed up with clinical breast examination at a more frequent interval. The role of frequent clinical breast examination appears more than mammography especially beyond 5 years for early detection of contralateral breast cancer.

Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Historically, a poor prognosis for metastatic disease has been reported with systemic chemotherapy. Significant advances have been made in the last decade, since the introduction of different tyrosine kinase inhibitors (TKIs). Unfortunately, even though the TKIs have been used for a long time, there are very few published data of the experience of TKI therapy in metastatic GIST from India. Materials and Methods: Patients diagnosed with metastatic GIST from January 2005 to October 2016 at our center, who received first-line therapy with imatinib 400 mg/day, were reviewed retrospectively. Patients profile, response to treatment, toxicity of TKI therapy, time to progression, and survival were evaluated. Results: Of the 44 metastatic GIST patients, 23 (52.2%) were males. Median age at diagnosis was 48 years. The most common presenting symptom was an abdominal pain (52%), followed by weight loss (23%). Most frequently affected metastatic site was liver (57%), followed by peritoneum (16%), and lungs (4.5%). Metastases to both liver and peritoneum were found in 10 patients (22.5%). All patients were initially treated with imatinib at a dose of 400 mg/day. Disease stabilization was documented in 21 cases (48%), and 13 patients (29%) achieved a partial response. TKI therapy was well-tolerated in most cases. Median progression-free survival (PFS) was 26 months, and estimated median survival was 48 months. Patients with lung metastases have a significantly inferior median PFS and overall survival, in comparison to patients with other metastatic sites (P < 0.05). Conclusions: Imatinib therapy was well tolerated and induced a sustained clinical benefit in more than half of the patients with metastatic GIST. Lung metastases seemed to be a poor prognostic factor in this patient population.

Induction chemotherapy in technically unresectable locally advanced T4a oral cavity squamous cell cancers: Experience from a regional cancer center of South India

Objectives: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in technically unresectable T4a oral cavity squamous cell cancers (OSCCs). Materials and Methods: Patients diagnosed with technically unresectable locally advanced T4a OSCC from January 2013 and November 2016 at our center, who received 2–3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients profile, response rates and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Results: Totally 80 patients received IC, and of them 58 (72.5%) were males. Median age at diagnosis was 44 years (range, 34–62 years). All our patients received IC with doublet regimen. Majority of the patients had buccal mucosa cancers (73.8%), followed by gingivobuccal complex (21.2%) and oral tongue (5%) primaries. After IC, partial response was achieved in 17 (21.3%) patients, stable disease in 49 (61.3%) patients and disease progression was noted in 14 (17.4%) patients. Post-IC, resectability was achieved in 19 (23.8%) of 80 patients, but 4 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 15) was 16.9 months (95% CI: 15.2–19.8 months) and for those treated with nonsurgical local therapy (n = 65) was 8.8 months (95% CI: 6.8–10.6 months) (log-rank P = 0.000). Conclusions: IC had a manageable toxicity profile and achieved resectability in 23.8% of our patients with technically unresectable T4a OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.

Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A single-institution experience from South India

Wide use and incorporation of newer diagnostic tools in the management of metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of personalized treatment of this disease. With the wide use of polymerase chain reaction and fluorescence in situ hybridization increasing number of patients are being diagnosed with dual and complex mutations posing a new challenge in the management of patient with metastatic NSCLC. In this article, we would like to bring forth six such cases and the varied responses to the current available treatment in patients with complex and dual mutations. The appropriate management in these groups of patients is yet to be standardized.

Induction chemotherapy in locally advanced T4b oral cavity squamous cell cancers: A regional cancer center experience

OBJECTIVESnThe present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in locally advanced T4b oral cavity squamous cell cancers (OSCCs).nnnMATERIALS AND METHODSnPatients diagnosed with locally advanced T4b OSCC from January 2013 to October 2016 at our center, who received 2-3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients profile, response, and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed by SPSS software version 17.nnnRESULTSnA total of 116 patients received IC, and out of them 90 (77.6%) were males. Median age at diagnosis was 43 years (range 31-62 years). Nearly 103 (88.8%) of our patients received doublet chemotherapy and the rest of the patients received triplet regimen. Majority of the patients had buccal mucosa cancers (71.6%), followed by gingivobuccal complex (21.6%) and oral tongue (6.9%) primaries. After IC, partial response was achieved in 20 (17.3%) patients, stable disease in 68 (58.6%) patients, and disease progression was noted in 28 (24.1%) patients. Post-IC, resectability was achieved in 22 (19%) of 116 patients, but 6 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 16) was 19.7 months (95% confidence interval [CI]: 16.0-22.8 months) and for those treated with nonsurgical local therapy (n = 100) was 7.1 months (95% CI: 5.8-8.2 months) (log-rank P = 0.000).nnnCONCLUSIONSnIC had a manageable toxicity profile and achieved resectability in 19% of our patients with T4b OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.

Multiple myeloma: Experience of an institute in limited resource setting

INTRODUCTIONnMultiple myeloma (MM) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The mainstay of treatment of myeloma is induction treatment followed by consolidation with autologous stem cell transplant (ASCT). However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT.nnnAIMnTo study the epidemiological features and outcome of MM patients treated in a limited resource setting.nnnMATERIALS AND METHODSnWe conducted a retrospective study at our institute to identify patients diagnosed as MM from 2005 to 2016. We studied the epidemiological profile and the outcome of the treatment in terms of response rates and overall survival.nnnSTATISTICAL ANALYSISnSurvival analysis was performed using Kaplan-Meier curve.nnnRESULTSnMedian age at diagnosis is 54 years (range: 39-85 years). IgG myeloma was the most common type seen in 72% of patients. The International Staging System (ISS) was ISS I (31%), ISS II (30%), and ISS III (39%). The median duration of treatment for thalidomide + dexamethasone (TD) and bortezomib + TD (VTD) was 9 and 7 months, respectively. Median survival for the TD versus VTD regimen (in a nontransplant setting) for the ISS I, ISS II, and ISS III groups was 49 and 55 months (P = 0.056), 42 and 48 months (P < 0.05), 21 and 27 months (P < 0.05), respectively.nnnCONCLUSIONnProteasome inhibitors significantly improved the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.

Efficacy and safety of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil regimens in locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma: A prospective phase II study from South India

BACKGROUNDnPatients with locally advanced inoperable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma have a poor prognosis. The maximum benefit of systemic chemotherapy is usually achieved in the first-line setting. Even though systemic chemotherapy has been used for long time, in view of unsatisfactory results, no standard regimen has been emerged. Unfortunately, till date, there is no published prospective data from India, comparing the two most commonly used triplet regimens, epirubicin, cisplatin plus 5-fluorouracil (ECF) and docetaxel, cisplatin plus 5-fluorouracil (DCF), in this patient population.nnnMATERIALS AND METHODSnThe present study aimed to compare the efficacy and safety of the first-line systemic chemotherapy with ECF and DCF regimens in locally advanced inoperable or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate, progression-free survival (PFS), and toxicity profile.nnnRESULTSnBetween January 2015 and December 2016, 58 patients were assigned and treated with ECF (n = 30) or DCF (n = 28) regimens. The median OS was 9.4 months with ECF and 12.5 months with DCF regimen (log-rank, P = 0.000), while median PFS was 5.8 and 7.5 months, respectively (log-rank, P = 0.002). Patients in the DCF arm had more frequent reductions in chemotherapy doses than those of the ECF arm (28.6% vs. 16.7%; P = 0.54). As compared with the ECF, the DCF regimen was associated with more frequent Grades 3-4 toxicities-neutropenia (16.7% vs. 39.3%, P = 0.17), febrile neutropenia (13.3% vs. 25%, P = 0.52), mucositis (6.7% vs. 17.8%, P = 0.43), and diarrhea (6.7% vs. 14.3%, P = 0.67).nnnCONCLUSIONSnIn comparison to ECF, the DCF regimen was associated with a statistically significant 3.1 months longer median OS without any significant increase in Grades 3-4 toxicities. DCF can be considered as one of the reference regimens, in properly selected patients with advanced/metastatic gastric or GEJ adenocarcinoma.