Discordance in clinical versus pathological staging in breast cancer: Are we undermining the significance of accurate preoperative staging in the present era?

BACKGROUND: The present era of individualized treatment for breast cancer is influenced by the initial disease status including the anatomical extent, grade, and receptor status. An accurate preoperative staging is the basis of treatment planning and prognostication. Our study aims to determine the discordance between the preoperative clinical and the postoperative pathological stages of breast cancer patients. METHODOLOGY: The medical records of all non-metastatic breast cancer patients from January 2017 to December 2018 who underwent upfront surgery were reviewed. They were staged as per the eighth AJCC and the concordance between the clinical (c) and pathological T (tumor), N (nodal), and final AJCC stage was studied. A Chi-square test was used to determine factors that significantly correlate with disease discordance. RESULTS: A total of 307 breast cancer patients were analyzed. Among these, 43.3% were hormone receptor-positive, 30.6% were Her2 positive and 26% were triple-negative. Overall stage discordance was seen in 48.5% (n = 149) patients (upstaging in 22.1%, downstaging in 26.4%). The discordance rate was 48.9% for T stage (cT versus pT) and 57.4% for N stage (cN versus pN). Among patients with clinically node-negative disease, 53.4% were found to have positive nodes on histopathology, while 27.2% had vice versa. Overall, the factors associated with upstaging were ER-positive, Her2 positive and triple-negative status (all p < 0.05), while none of the factors showed significant association with downstaging. CONCLUSIONS: About half of breast cancer patients had discordance between clinical and pathological staging with higher discordance in the nodal stage. This changes the disease prognosis, and may also affect the offered surgical treatment and radiotherapy. Thus highlighting the need for a precise pre-operative staging. Also, this information will aid clinicians in discussions with patients, keeping in mind the likelihood of change in disease staging and management.

Socioeconomic and administrative factors associated with treatment delay of esophageal and gastric carcinoma: Prospective study from a tertiary care centre in a developing country.

This study was aimed to analyze the spectrum of time intervals, from the onset of symptoms to the commencement of treatment in esophagogastric cancers. Factors influencing these time delays and correlation between these time points with variables including socioeconomic strata, educational level, histopathology, location of tumor and the initial modality of treatment were assessed. STUDY SETTING AND METHODS: A prospective analysis of patients with esophagogastric cancer presenting to a single tertiary care unit over a period of 12 months was performed. Histopathology other than adenocarcinoma and squamous cell were excluded. RESULTS: 202 patients were enrolled in the study. Most patients presented with advanced disease, i.e. 91.5 % of esophageal and 90 % of gastric malignancies belonged to either stage 3 or stage 4 as per American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The median delay from the appearance of the first symptoms to initiation of treatment was 15 weeks (range 4-64). Patient related factors contributed to a significant delay [median of 5 weeks (range 1-24)]. Administrative factors were responsible for median delay of 3 weeks (range 0.5-20). Curative multimodality treatment was administered in 62.5 % of patients. Significant longer delay was influenced by socioeconomic strata, educational level, evaluation by non-specialist (p < 0.05). No relationship was noted between histopathology, location of tumor or initial modality of treatment. CONCLUSIONS: Delays in our setting is much more than that is seen in Western and even some Asian countries. An important component of delay is administrative related factors. These may be intervened at the hospital level compared to other factors which may need long term community oriented approaches.

Clinical profile, cytogenetics and treatment outcomes of adult acute myeloid leukemia.

INTRODUCTION AND AIMS: Acute myeloid leukemia (AML) in adults has poor prognosis. The epidemiologic profile of patients varies greatly in different geographic locations and so do the cytogenetic abnormalities and the FAB subtype of the AML. We intended to study the clinical profile, cytogenetics, and outcomes with standard of care treatment on our population in India. METHODS: This was a retrospective study with systematic review of 203 case records. Primary objectives were to know the demographic profile of AML, prevalence of various FAB subtypes, cytogenetic abnormalities, and treatment outcomes at our center, which is a referral center of oncology. Two treatment outcomes considered in study for patients of AML were achievement of remission status of the bone marrow postintensive induction chemotherapy and sustenance of the remission for 6 months, once remission is achieved. Secondary objective was to study these outcomes in non-M3 AML in relation to cytogenetics. RESULTS: Median age was 39 years. The most common FAB subtype observed was AML M2. About 65.6% patients achieved complete remission (CR), and 42.4% patients could sustain it for next 6 months. Cytogenetics correlated with prognosis but not age. CONCLUSIONS: Our population differs from the Western population regarding lower age, lower prevalence of adverse cytogenetics, and higher prevalence of favorable cytogenetic abnormalities. Cytogenetics had a good correlation with CR rates after chemotherapy as well as its sustenance.

Follicular lymphoma transforming to DLBCL and reverting back to follicular lymphoma at relapse-a case report.

BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

HIV/AIDS-related lymphoma: perspective from a regional cancer center in India.

BACKGROUND: India has the third largest population of people living with HIV/AIDS (PLHA). Lymphoma is the second most common malignancy among PLHA. However, data are lacking regarding HIV/AIDS-related lymphoma (ARL) in India. This study evaluated the epidemiology and clinical outcomes of ARL from a regional cancer center in India. METHODS: This retrospective analysis included cases of ARL between March 2011 and September 2017. Data were obtained from patient record files for the assessment of epidemiology and clinical outcomes. Statistical analysis was performed using GraphPad Prism 6. Comparisons of subtype-specific survivals were performed using log-rank tests. RESULTS: Of 1,226 lymphoma cases, 80 (6.5%) were ARL. Details were available for 70 patients. The median age at diagnosis was 40.5 (9-74) years with a male:female ratio of 2:1. AIDS-defining lymphomas (ADL) constituted 78.6% of cases, while 21.4% had non-AIDS defining lymphoma (NADL). The mean CD4 counts were 193.15±92.85 and 301.93±107.95 cells/µL, respectively (t-test; P=0.0002). Extranodal involvement was present in 55.7%, B symptoms were reported in 60%, and lactate dehydrogenase (LDH) was elevated in 64.3% of patients. The median overall survival times were 6 months for plasmablastic lymphoma (PBL), 23 months for diffuse large B-cell lymphoma (DLBCL), and was not reached for Hodgkin's lymphoma (log-rank test; P=0.0011). Other histological subtype cases were too few to draw meaningful survival outcomes. CONCLUSION: ARL is a heterogeneous disease. Histologic subtype is a major determinant of the clinical outcome. ADL has significantly lower CD4 counts than those of NADL. There is an urgent and unmet need for uniform management guidelines for improving outcomes in this under-represented patient population.

Modified Epirubicin, cisplatin, and 5-FU regimen as first-line chemotherapy in metastatic gastric or gastroesophageal junction adenocarcinoma: A Phase II study.

BACKGROUND: Epirubicin, cisplatin, and 5-FU (ECF) is one of the most commonly used first-line chemotherapy regimens in metastatic gastric cancer. However, due to protracted infusion schedule, need for special infusion pumps, and catheter-related complications, the practical utility and acceptability of standard ECF regimen are limited, particularly in resource-constrained settings including India. MATERIALS AND METHODS: In the present study, we have used a more convenient modification of the standard ECF protocol (using 5 days intravenous infusion of 5-FU at a dose of 750 mg/m2/day, given over 6 h through a peripheral venous line), in Indian patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and toxicity profile. RESULTS: Between January 2014 and December 2017, 107 patients were assigned and treated with this modified ECF regimen. The median age was 52 years (range, 34-62); 66.3% were males and 36.5% of the patients had ≥ 3 metastatic disease site involvement at baseline. Dose reductions due to toxicity were required in 14.9% of the patients. The ORR was 32.7%; median PFS and OS were 5.9 months (95% confidence interval [CI]: 4.7-6.9) and 10.4 months (95% CI: 8.4-11.8), respectively. Both the hematological and nonhematological toxicities were manageable, and there was no toxicity-related death. The most frequent Grade 3-4 adverse events were neutropenia (18.7%), febrile neutropenia (13.1%), mucositis (5.6%), and diarrhea (5.6%). CONCLUSIONS: In the present study, the modified ECF regimen demonstrated significant efficacy with an acceptable toxicity profile in Indian patients with metastatic gastric and GEJ adenocarcinoma. The survival outcomes of this modified schedule were comparable with those of the standard ECF regimen, as reported earlier. Clearly, this modified and more convenient ECF protocol should be explored and validated through large prospective randomized trials.

Correlation of BMI with breast cancer subtype and tumour size.

BACKGROUND: Breast cancer is a heterogeneous disease which is divided broadly into luminal, HER2 and basal type based on molecular profiling. Increased body mass index (BMI) has been associated with the risk of developing breast cancer but the association based on molecular subtype remains conflicting. METHODS: This was an observational study carried out over a period of 2 years. Nonmetastatic breast cancer patients were evaluated for the tumour subtype based on surrogate markers (ER, PR and HER2). The BMI of these patients was correlated with the tumour subtype and size. RESULTS: We studied 476 patients with breast cancer with the median age of 46 years (range, 25-86) and 58% were premenopausal. The mean BMI of the cohort was 24.1, which was significantly higher in postmenopausal women (24.9 versus 23.6, p < 0.05). Overall, only 10% of patients were obese. The mean BMI in the luminal, HER2 and TNBC subtypes was 24.7, 22.4 and 23.9, respectively (p < 0.01). Also, the mean tumour size in luminal, HER2 and TNBC subtype was 4.02, 3.80 and 4.27 cm, respectively (p = 0.158). CONCLUSION: The average BMI was higher in patients with luminal subtype followed by TNBC and lowest for HER2 at the time of diagnosis. The mean tumour size was numerically higher for TNBC and lowest for HER2 subtype although the difference was not statistically significant. Larger studies may provide clarity of association between the BMI and tumour subtype.

Comparison of health-related quality of life with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil chemotherapy regimens as first-line systemic therapy in locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma: A prospective study from South India.

BACKGROUND: Health-related quality of life (HRQOL) is an important oncologic end point for upper gastrointestinal malignancies. Unfortunately, till date, there is no published prospective data from India, comparing the HRQOL parameters between first-line chemotherapy regimens in advanced/metastatic gastric cancer. MATERIALS AND METHODS: The present study aimed to compare the HRQOL of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-FU (ECF) and docetaxel, cisplatin plus 5-FU (DCF) regimens in patients with locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma. The secondary end points were overall response rate, progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: Between December 2014 and December 2016, 65 patients were treated with ECF (n = 34) or DCF (n = 31) regimen. The baseline HRQOL scores were comparable between the two study groups, with the exception of significantly poor pain and sleep difficulties symptom score in the DCF group. After three cycles of treatment, both the groups showed improvements in most of the quality of life (QOL) parameters including global QOL score, compared with their baseline status. After six cycles of chemotherapy, the ECF group showed nonsignificant deterioration for most of the QOL parameters; but on the contrary, the DCF group maintained improved scores for most of the QOL parameters. The median survival until a definitive deterioration of global QOL score was significantly better in the DCF arm in comparison to the ECF arm (7.1 vs. 5.6 months, respectively, P = 0.000). The median OS was 9.2 months with ECF and 12.5 months with DCF regimen (P = 0.000), while median PFS was 5.7 and 7.4 months with ECF and DCF regimens, respectively (P = 0.002). CONCLUSIONS: This prospective study highlighted a better impact of DCF chemotherapy on the HRQOL of patients with advanced/metastatic gastric cancer and showed the importance of QOL assessments in clinical trials to complement the risk-benefit judgment.

Primary breast angiosarcoma - a single institution experience from a tertiary cancer center in South India.

INTRODUCTION: Primary angiosarcoma of the breast is a rare entity with incidence of less than 0.05% of all malignant breast neoplasms. It occurs in young females without any associated risk factors. The tumor behaves aggressively and has a poor prognosis compared to invasive ductal carcinoma. METHOD: It was a retrospective observational study done at a tertiary cancer center from January 2012 to December 2016. The medical records of patients diagnosed with primary breast angiosarcoma were reviewed for the study. Clinicopathological profile, treatment, and the outcomes were analyzed. RESULTS: Four patients were diagnosed with primary breast angiosarcoma out of 2560 breast cancer patients seen over a period of 5 years. Two had metastatic disease at presentation. Among four patients, two underwent surgery of the primary tumor, whereas, all received chemotherapy either as adjuvant or palliative setting. One patient received adjuvant radiation therapy. Three patients received 2nd line and one received 3rd line chemotherapy on disease progression. After a median follow-up of 18 months one patient was surviving on 3rd line chemotherapy with trabectedin. Other three succumbed to disease after progression. CONCLUSION: Due to a small number of this malignancy randomized studies are difficult to perform and optimum treatment strategy still need to be defined.

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma in adults: Results from a nonendemic region.

BACKGROUND: Recently published prospective clinical trials and two meta-analyses have shown that addition of induction chemotherapy (IC) to concurrent chemoradiation (CRT) could potentially improve outcomes in comparison to CRT alone, in locoregionally advanced nasopharyngeal carcinoma (LANPC). Although it remains unclear which is the best IC regimen to be offered and for how many cycles. Unfortunately, till date, there are no published data from India regarding the outcomes of various commonly used IC regimens before CRT, in LANPC. MATERIALS AND METHODS: Patients diagnosed with LANPC from January 2012 to December 2017, who received three cycles of IC before definitive CRT were reviewed retrospectively. Patients' profile, toxicity of IC, response rates, failure-free survival, and overall survival (OS) were evaluated. RESULTS: A total 34 patients with LANPC who received IC were reviewed. The median age at diagnosis was 36 years, and the majority were males (67.6%, n = 23). Nineteen patients received IC with paclitaxel plus cisplatin regimen (TP) and the remaining 15 patients received IC with docetaxel/paclitaxel plus cisplatin plus 5-FU regimen (TPF). The overall response rates after three cycles of TP and TPF IC were 68.4% and 80%, respectively, and the corresponding rates were 84.2%and 93.3%, respectively, 2 months after completion of CRT. At a median follow-up of 24 months, 2-year failure-free survival and OS for TP arm were 78.9% and 89.5%, and the corresponding rates for TPF arm were 86.7% and 93.3%, respectively. All Grade III-IV toxicities were numerically higher with triplet IC regimen in comparison to doublet regimen. CONCLUSION: In this retrospective analysis, there was no significant difference between taxane-based doublet and triplet IC regimens, in terms of survival outcomes, although Grade III-IV toxicities were numerically higher with triplet IC regimen. Clearly, these hypothesis-generating findings should be tested in a prospective randomized setting.

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

OBJECTIVES: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in locally advanced T4b oral cavity squamous cell cancers (OSCCs). MATERIALS AND METHODS: Patients 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. RESULTS: A 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). CONCLUSIONS: IC 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.

INTRODUCTION: Multiple 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. AIM: To study the epidemiological features and outcome of MM patients treated in a limited resource setting. MATERIALS AND METHODS: We 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. STATISTICAL ANALYSIS: Survival analysis was performed using Kaplan-Meier curve. RESULTS: Median 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. CONCLUSION: Proteasome inhibitors significantly improved the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.

Patterns and the Occurrence of KRAS Mutations in Metastatic Colorectal Cancers-a Study from Indian Regional Cancer Centre.

Mutation analysis of the KRAS oncogene is established as a predictive biomarker in Colorectal cancer (CRC). Many prospective clinical trials have shown that only CRCs with wild-type KRAS respond to anti-epidermal growth factor receptor (EGFR) treatment. Hence, mutation analysis is mandatory before treatment of metastatic CRCs. There are very few studies on the KRAS mutation status in the Indian setting. Hence, this study was done to document the patterns of KRAS mutations in CRCs reporting to a regional cancer centre in South India. Among 150 cases of metastatic colorectal cancer reporting over a period of 20 months, 48 random cases were analyzed for the KRAS mutational status of codons 12 and 13 of the KRAS gene by genomic sequencing. KRAS mutations in codons 12 and 13 were present in 9/48 (18.75%) of all analyzed CRCs. The common types of mutations were glycine to aspartate on codon 12 (p.G12D), glycine to valine on codon 12 (p.G12 V), and glycine to aspartate on codon 13 (p.G13D).

A rare case of primary synovial sarcoma of lung.

Synovial sarcoma of lung is a very rare tumor accounting for 0.5% of all primary lung malignancy. It presents clinically with cough, chest pain, shortness of breath, or hemoptysis, with a mass lesion on X-ray and computerized tomography scan. Diagnosis is made by histopathology and immunohistochemistry. Here, we report a case of 48-year-old male, who presented with right-sided chest pain, cough with blood-tinged sputum, and found to have primary pulmonary synovial sarcoma of lung.

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.

Colorectal cancer presenting as bone metastasis.

INTRODUCTION: Bone metastasis is a rare site of metastasis, seen in only 3.7-11% of clinical cases. Isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare. OBJECTIVES: To discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with survival in patients of colorectal cancer that have bone metastasis at the time of presentation. MATERIALS AND METHODS: Retrospectively, tumor registry was analyzed for the cases of colorectal cancer presenting with bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan-Meier method and analyzed using the log-rank test. RESULTS: Ten such patients were identified (male:female = 7:3) of the total 410 patients. Median age was 41 years (22-50 years). All patients were Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

Myelomatous pleural effusion: A rare case entity reported from a tertiary care cancer center in South India.

Multiple myeloma (MM) is a plasma cell neoplasm and constitutes 10% of hematologic malignancies. Malignant myelomatous pleural effusions are very rare and occur in <1% of cases of MM. In this article, we report a rare case of a patient who initially presented with pleural effusion and was subsequently found to be secondary to MM with an underlying raised IgG paraprotein. The patient symptomatically improved and was in partial remission with palliative radiotherapy, VTD chemotherapy, and bisphosphonates.

Advanced hepatocellular carcinoma: A regional cancer center experience of 48 cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health burden and the seventh most common cause of cancer-related death in India. Patients with advanced unresectable HCC have a poor prognosis with a reported median survival of only 2-3 months with the best supportive care (BSC). Sorafenib is the only drug that has demonstrated a survival benefit over BSC in advanced HCC. Unfortunately, even though it has been used for a long time, there are very few published data regarding the experience of sorafenib therapy in advanced HCC from India. MATERIALS AND METHODS: Patients diagnosed with advanced HCC from January 2012 to July 2017 at our center were reviewed retrospectively. Patients' profile, time to progression, survival, and toxicity of sorafenib therapy were evaluated. RESULTS: Of the 48 advanced patients with HCC, 35 (72.9%) were male. The median age at diagnosis was 52 years. The most common presenting symptom was abdominal pain (77%, n = 37), followed by abdominal distension (37.5%, n = 18), loss of appetite and/or weight (33.3%, n = 16), and jaundice (16.7%, n = 8). Hepatitis B virus infection was documented in 37 patients (77%), whereas 4 patients had hepatitis C virus infection. Patients were treated with standard dose sorafenib (n = 30), BSC alone (n = 14), or transarterial chemoembolization followed by sorafenib (n = 4). Sorafenib therapy was well-tolerated in most cases. The median progression-free survival with upfront sorafenib was 4.3 months. The median overall survival (OS) of the patients who received upfront sorafenib was significantly better than those treated with BSC alone (5.9 vs 3.0 months; log-rank P= 0.00). CONCLUSION: Sorafenib therapy was well-tolerated and provided about 3 months longer median OS in our patients with advanced HCC than those treated with BSC alone.

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.

Safety and antitumor activity of arsenic trioxide plus infusional 5-fluorouracil, leucovorin, and irinotecan as second-line chemotherapy for refractory metastatic colorectal cancer: A pilot study from South India.

BACKGROUND: After failing oxaliplatin-based first-line chemotherapy (CT), approximately 4%-21% of patients with metastatic colorectal cancer (mCRC) respond to irinotecan-based second-line treatment. Earlier studies have demonstrated that arsenic trioxide (ATO) can significantly resensitize resistant colon cancer to 5-fluorouracil (5-FU) by downregulating thymidylate synthase (TS). We hypothesized that a combination of ATO with infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) regimen in mCRC patients refractory to first-line FOLFOX/CAPOX could further improve the outcome of second-line CT. MATERIALS AND METHODS: Patients were administered ATO 0.15 mg/kg/day on days 1-2 along with FOLFIRI regimen at standard doses every 2 weeks, until disease progression, unacceptable toxicity, or patients' refusal. Responses to CT were reported according to RECIST 1.1. Adverse events were classified based on CTCAE version 4.0. RESULTS: Between September 2016 and July 2017, 17 patients with refractory mCRC were treated with this investigational combination. The median age was 49 years; 13 males and 4 females; ECOG PS 0-1/2, 14/3. The most common site of metastases was liver (n = 11) followed by peritoneum (n = 7) and number of involved metastatic sites 1-2/≥3, 9/8. After 6 cycles of CT, overall response rate and disease control rate were 17.6% and 82.4%, respectively (complete remission = 0, partial remission = 3 patients, stable disease = 11 patients). Median progression-free survival was 5.3 months (95% confidence interval [CI]: 4.3-7.0) and median overall survival was 9 months (95% CI: 7.4-10.5) from the initiation of ATO plus FOLFIRI. The toxicities were as follows: Grade 1/2 toxicity: fatigue (7 patients), constipation (2), and nausea and vomiting (2); Grade 3 toxicity: fatigue (3), neutropenia (2), febrile neutropenia (1), diarrhea (2), and QTc prolongation (1). No patient experienced Grade 4 toxicities. CONCLUSIONS: The addition of ATO to FOLFIRI regimen as second-line CT in patients with refractory mCRC offered an encouraging antitumor effect at the cost of manageable toxicity.