Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients-a real-world experience from India.

Elderly patients with acute myeloid leukemia have a poor prognosis. Data from developing countries is sparse in the literature. In this retrospective study, 402 patients aged ≥ 60 years, diagnosed between Jan 2013 and Dec 2017, were analyzed for treatment patterns and survival. Median age of the whole cohort was 68 years (range 61-84). A total of 213 patients (53.3%) refused care; 188 patients (46.7%) received either BSC, LDAC, or HMA. Survival (in months) was 3.9, 6.4, and 1.2 with LDAC, HMA, and BSC, respectively. One-year survival was 17.2% and 6% with HMA and LDAC, respectively (P = 0.02). Overall response rate (ORR) did not differ between HMA and LDAC group (p = 0.12). HMA cohort had higher complete responses (20.6% vs 7.4%, p = 0.02), stable disease (32.7% vs 13.5%, p = 0.02), and transfusion independence (TI) (46.5% vs 22.2%, p = 0.01). Survival did not differ between the groups if the patients achieved ORR (12.3 vs 9.8 p = 0.2) or TI (11.6 vs 6.4 p = 0.2). Stable disease with HMA led to longer survival (8.1 vs 5.3 p = 0.01). HMAs were more effective than LDAC irrespective of cytogenetic risk category and blasts, of note HMAs improved survival of poor risk patients (5.6 vs 2.9 p = 0.004). HMA treatment (HR = 0.48; 95% 0.29-0.79, p = 0.004) and transfusion independence (HR = 0.2; 95% 0.1-0.3, p = 0.0001) predicted survival in multivariate analysis. Neutropenia and febrile neutropenia were frequent in HMA. Thrombocytopenia was the common adverse event with LDAC. Novel and cost-effective drugs are essential to improve the prognosis of these patients.

Adult Philadelphia-Positive Acute Lymphoblastic Leukemia: A Single-Institution Experience in Limited-Resource Setting.

L. K. RajeevBackground Adult Philadelphia-positive (Ph + ) acute lymphoblastic leukemia (ALL) is a distinct entity with poor prognosis. Treatment with tyrosine kinase inhibitors improved responses but still with poor outcomes. We evaluated treatment outcomes in these patients treated in limited-resource settings in the absence of availability of allogeneic stem cell transplantation (ASCT). Materials and Methods We studied case record files of the adult patients diagnosed with Ph+ ALL. Results A total of 18 patients were evaluated retrospectively. The median age of presentation was 28 years. Male-to-female ratio was 1:1. Patients presented with fever and fatigue. Six patients (33.33%) presented with cervical lymphadenopathy. Clinical splenomegaly was present in 16 (88.88%) patients on palpation, whereas on ultrasonographic evaluation, all 18 patients had splenomegaly. The median size of the spleen was 15 cm. Hepatomegaly was seen in 5 (27%) patients. All 18 patients had anemia at the time of presentation. Leukocytosis was seen in 17 (94.44%) patients, whereas 1 (5.56%) patient presented with low total leukocyte count. The median platelet count at the time of presentation was 30,000/mm. 3 On peripheral smear, median number of blast cells was 55%, and on bone marrow aspiration samples, median blast percentage seen was 70%. Conventional cytogenetics was done in all the patients on bone marrow aspiration samples. Ten patients (55.55%) had t(9;22) - Ph chromosome. One patient (5.56%) on cytogenetics showed double Ph chromosome. The median value of breakpoint cluster region-ABL1 transcript in IS% was 13%. Seventeen (94.44%) received ALL protocol (BFM95) along with tyrosine kinase inhibitor (imatinib). One (5.56%) patient refused aggressive cytotoxic chemotherapy. No patient underwent ASCT. The median duration of follow-up was 7.5 months, ranging from 3 to 16 months. Median overall survival (OS) was 7.5 months and 2-year OS was 33.33%. Conclusion Poor prognosis of this disease, especially in the absence of ASCT, remains a major challenge in the treatment.

Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of ßIII-tubulin expression as a predictive marker.

BACKGROUND: This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of ßIII-tubulin as a predictive marker was also evaluated. PATIENTS AND METHODS: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12 weeks (n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. ßIII-Tubulin expression was assessed using immunohistochemistry. RESULTS: There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6-30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4-31.7). ßIII-Tubulin-positive patients obtained higher pCR rates compared with ßIII-tubulin-negative patients in both treatment arms; however, ßIII-tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy. CONCLUSIONS: Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among ßIII-tubulin-positive patients.

Double Philadelphia Chromosomes- A Rare, Yet an Important Cytogenetic Phenomenon of Prognostic Significance in De Novo Acute Lymphoblastic Leukemia.

Presence of additional copies of Philadelphia chromosome (Ph) is characteristic of chronic myeloid leukemia in blast crisis, very rarely observed in de novo acute lymphoblastic leukemia (ALL). Ph positive (Ph+ve) ALL and CML in lymphoid blast crisis (CML-LBC) are biologically different with divergent clinical course. Double Ph+ve ALL has little data available as to its incidence and prognostic significance. We studied five cases of Ph+ve precursor B-cell ALL having an extra copy of Ph chromosome with regard to their clinical and laboratory features. An extensive review of literature was done on prognostic significance and molecular aspects of double Ph in ALL. The study confirms that double Ph was a rare phenomenon in precursor B-cell ALL. It is observed that molecular basis of double Ph positive ALL is less understood compared to CML in blast crisis. The study highlights fundamental role of cytogenetic and molecular studies in diagnosis and management of these patients. Long-term follow-up studies on a larger group of patients are required to understand the prognostic impact of extra Ph in Ph+ve ALL, which is usually resistant to standard chemotherapeutic regimen and often requiring bone marrow transplantation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01525-1.

Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

Lymphoma that on morphology appear blastoid or intermediate between DLBCL and BL but who lack myc and bcl-2 and/or bcl-6 rearrangements are grouped under high grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Only a few studies have yet compared the outcome of HGBL, NOS treated with different chemo-immunotherapy regimens. HGBL, NOS patients were analyzed retrospectively, who were treated with CHOP or DAEPOCH regimens every 21 days for six cycles with or without rituximab. The primary clinical objective was progression free survival. One and two year PFS rates were 29.4% and 20.6% for the CHOP arm and, 65.2% and 47.8% for the DAEPOCH arm respectively. There was statistically significant difference in mean PFS between the arms (DAEPOCH vs CHOP: 19.7 months vs 12.8 months; HR = 0.44, p = 0.02, 95% CI: 0.22-0.88). One and two year OS rates were 91.1% and 20.5% for the CHOP arm and 95.6% and 60.8% for the DAEPOCH arm respectively. Mean OS was significantly better for DAEPOCH arm (28.1 months vs 20.7 months: HR = 0.43, p = 0.03, 95% CI: 0.20-0.92). Grade 3 and 4 hematological and non-hematological toxicities were more common in DAEPOCH arm. There were 2 treatment related deaths, 1 in each arm (4.3% for DAEPOCH vs 2.9% for CHOP). HGBL, NOS is a heterogeneous group of aggressive lymphoma associated with early relapse in nearly half of the cases. Intensive regimens like DAEPOCH is associated with improved outcome in terms of PFS and OS. Though toxicities are more with DAEPOCH, they are manageable and treatment related mortality is low.

Rapidly Progressing Plasma Cell Leukemia with Underlying Plasmablastic Morphology: A Rare Case Report of a 25-Year Old Male.

Multiple myeloma constitutes a wide spectrum of diseases, ranging from slow-growing monoclonal gammopathy of undetermined significance to rapidly progressing plasma cell leukemia. It is a very rarely diagnosed hematological malignancy in those less than 30 years of age. A 25-year-old male presented with complaints of fatigue and low-grade fever. On investigation, he was found to have bicytopeina and features of tumor lysis syndrome. Initially, this was thought to be indicative of acute leukemia. However, upon further analysis with bone marrow biopsy, serum protein electrophoresis, and immunofixation, it was determined that the patient had an IgG myeloma with plasmablastic morphology. It rapidly progressed and the peripheral smear started showing clusters of plasma cells suggesting a picture of plasma cell leukemia. The patient succumbed to this aggressive disease despite treatment. This case illustrates that myeloma should also be included in the differential diagnosis for young patients, especially the rare plasmablastic variant, which can be misdiagnosed as acute leukemia. The aggressive morphology also tends to show rapid progression to plasma cell leukemia, which has a poor prognosis.

Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid.

Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

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.

Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung.

BACKGROUND: Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA). MATERIALS AND METHODS: In this prospective observational study, patients with squamous cell carcinoma lung, either newly diagnosed or having a progressive disease on prior therapy were eligible. Cf-DNA was extracted from peripheral blood and analyzed for EGFR, KRAS, NRAS, and BRAF mutations using NGS. RESULTS: Sixteen patients were enrolled over a period of 1 month. The mean cf-DNA quantity extracted from the plasma was 96.5 ng (range, 15-200 ng). Eight clinically relevant mutations in the EGFR pathway were identified. These include Exon 21 mutations in 4 patients, Exon 20 mutation in onepatient, complex mutations with coexisting Exon 21 and Exon18 in one patient and KRAS Exon 2 mutations in two patients. CONCLUSION: cf-DNA is a minimally invasive technique for detection of clinically relevant mutations in lung cancer patients. The use of novel advanced techniques such as NGS may help in detecting EGFR pathway mutations in patients with squamous cell carcinoma lung.

Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study.

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.

Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer.

BACKGROUND: Lapatinib (L) plus trastuzumab (T) with weekly paclitaxel significantly increased the pathologic complete response (pCR) rate compared with the anti-human epidermal growth factor receptor 2 (HER2) agent alone plus paclitaxel. The event-free survival (EFS) and overall survival (OS) by the treatment arms L + T vs. T and L vs. T and the relationship between pCR and EFS/OS both in the whole study population and according to hormone receptor-negative and hormone receptor-positive cohorts after a median follow-up of 6.7 years were assessed. PATIENTS AND METHODS: Four hundred fifty-five patients with HER2-positive early breast cancer randomly received L 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. After surgery, patients received 3 cycles of fluorouracil, epirubicin and cyclophosphamide. The primary end-point was pCR (ypT0/is; for current analysis, it is ypT0/is ypN0), and the secondary end-points were EFS and OS. RESULTS: Six-year EFS rates were 67%, 67% and 74% with L, T and L + T, respectively (L vs T: hazard ratio [HR], 0.98 [95% confidence interval {CI}, 0.64-1.51; P = .93]; L + T vs T: HR, 0.81 [95% CI, 0.52-1.26; P = .35]). Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]). In landmark analyses, patients with a pCR had a significantly higher 6-year EFS (77% and 65%) and OS (89% and 77%) compared with those without a pCR for both overall and the hormone receptor-negative cohort. CONCLUSION: Achieving a pCR is important in HER2-positive disease and translates into better long-term outcome with regard to EFS and OS.

Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma whose outcomes have significantly improved with rituximab in addition to anthracycline-based chemotherapy. OBJECTIVE: This study aimed to study the epidemiology, treatment, and outcomes of patients with DLBCL. MATERIALS AND METHODS: A total of 526 patients diagnosed with DLBCL between 2006 and 2015 were retrospectively analyzed. RESULTS: The median age was 50 years with a male preponderance. Two hundred and twenty-three (42.39%) patients presented with B symptoms. A total of 53 (10.07%) patients presented with bulky disease and 202 (31.40%) with extranodal disease. The most common extranodal sites involved were the stomach (20.79%) and the bone marrow (10.89%). Bone marrow involvement was seen in only 22 (4.18%) cases. The distribution of patients presenting in low, low-intermediate, high-intermediate, and high-risk International Prognostic Index (IPI) were 148 (28.13%), 191 (36.31%), 124 (23.57%), and 63 (11.97%), respectively. The median survival of the entire cohort was 22 months. Survival of patients that compared the two groups with respect to the IPI - one having clubbed patients in low and low/intermediate risk and the other clubbing high/intermediate and high risk showed significantly improved survival in the lower risk groups - 24 versus 18 months (P = 0). The survival of those who received chemoimmunotherapy i.e R - CHOP was significantly better than those who received chemotherapy (CHOP) alone - 33 versus 21 months (P = 2.22e-16). CONCLUSIONS: DLBCL is one of the most common lymphomas seen in our daily practice. Outcomes are significantly inferior compared to western countries. Biological and patient-related factors such as nongerminal center B subtype, higher extranodal involvement, and poor tolerability to treatment could contribute to inferior outcomes.

Metastatic thymic epithelial tumors: A regional cancer center experience.

BACKGROUND: Thymic epithelial tumors (TET) are the most common tumors of the anterior mediastinum. Patients with advanced/metastatic disease are usually treated with palliative chemotherapy (CT). Unfortunately, even though various palliative CT regimens have been used for long time, there is a real scarcity of published Indian data regarding the experience of palliative CT in metastatic TET (mTET). MATERIALS AND METHODS: This is a retrospective analysis of mTET patients treated between January 2010 and September 2017. Patients who received at least three cycles of first-line palliative CT were included for analysis of response rates, toxicity, and survival and prognostic factors. RESULTS: Of the 49 mTET patients, 27 (55.1%) were males. The median age at diagnosis was 52 years (range: 25-65). Eighteen patients (36.7%) had Masaoka Stage IVa disease, and the rest of the patients had IVb disease. The most common site of metastasis was pleuropericardium (n = 18), followed by lungs (n = 16) and lymph nodes (n = 9). The median progression-free survival and overall survival (OS) were 11.2 months (95% confidence interval [CI], 8.7-13.6) and 20.2 months (95% CI, 17.1-22.8), respectively, for the whole cohort (n = 49). The median OS of patients with Stage IVa disease was significantly better than that of the patients with Stage IVb disease (log-rank P = 0.000). Moreover, the "responders" to first-line CT had a significantly better median OS than the "nonresponders" (log-rank P = 0.000). Various first-line palliative CT regimens were well tolerated in our patients. CONCLUSION: Adriamycin Cisplatin Vincristine Cyclophosphamide (ADOC), Cyclophosphamide Adriamycin Cisplatin, and paclitaxel + carboplatin all are viable first-line palliative CT options for mTET and showed a comparable survival in Indian patients. The present study suggested that "responders" to first-line CT and those with Stage IVa disease might have a better survival than "nonresponders" and those with Stage IVb disease, respectively.

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.

Is Colorectal Cancer in Young (<40 Years) Different from those in the Elderly (>40 Years): Experience from a Regional Care Center.

BACKGROUND: Colorectal cancer (CRC) is considered a disease of elderly. There has been a steady decrease in the incidence in those aged >50 years, with an alarming increase noted in adults aged <50 years. SUBJECTS AND METHODS: We retrospectively analyzed 89 patients diagnosed with CRC aged <40 years between the years 2010 and 2014. Their clinical profile, treatment, and outcomes were studied. RESULTS: The median age was 33 years with a male preponderance (56.2%). Most common symptoms were lower gastrointestinal bleed (48.3%) followed by abdominal pain (46.1%). Most common sites were rectum (50.6%) followed by colon. Histology in all was adenocarcinoma. Most tumors were moderately differentiated (54%) and were stage 4 (36%). Most common sites of metastases were liver (46.9%) followed by peritoneum and ovaries. Majority underwent surgery with adjuvant chemotherapy, with/without radiotherapy. Chemotherapy was administered in 70 patients, majority receiving FOLFOX-4 regimen (88.6%). Median survival was 23 months. Survival in early stage[1],[2] was significantly higher than in advanced stages (3 and above), 34 and 19 months (P = 0.0287), in those aged >40 years compared to <40-35 versus 23 months (P = 0.0029), nonmetastatic compared to metastatic disease - 26 versus 14 months (P = 0.00196), and females compared to males - 26 and 18 months (P = 0.0242). There was no significant difference in survival with respect to tumor grade or site of metastases (hepatic versus extrahepatic). CONCLUSIONS: Colorectal carcinoma in young seems to be an emerging problem in India. Any young patient presenting with symptoms suggestive of a colonic malignancy should be evaluated promptly and treated aggressively.

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India.

CONTEXT: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. SETTINGS AND DESIGN: Retrospective analysis. MATERIALS AND METHODS: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. RESULTS: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3-4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. STATISTICAL ANALYSIS USED: SPSS software version 20. CONCLUSION: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted.

Predictive and Prognostic Implications of Variant Philadelphia Translocations in CML: Experience From a Tertiary Oncology Center in Southern India.

INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results. MATERIALS AND METHODS: We retrospectively analyzed our data from January 2002 to December 2014. Patients with vPh in chronic phase of CML (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival and their data were compared with data of patients with classical Ph translocation (cPh). RESULTS: Of 615 patients diagnosed with CML-CP, 72 patients (11.7%) showed vPh. Most common chromosomes involved in these translocations were 14 (13.9%), 11 (12.5%), 19 (9.7%), and 7 (8.3%). Rates of complete hematological response, complete cytogenetic response, and major molecular response were not statistically different between the groups. At 5 years, event-free survival, failure-free survival, progression-free survival, and overall survival were 60% versus 67.9%, 62.7% versus 69.7%, 84.7% versus 92.1%, and 87.5% versus 92.4%, respectively, in vPh and cPh. The differences in survival were statistically not significant. CONCLUSION: To our knowledge, this is the largest series of variant translocations in CML-CP, pertaining to the Indian population. Our data suggest that the presence of vPh in CML has no significant effect in predicting response to imatinib as well as in prognosticating survival.

Performance of Sokal and Eutos Scores for Predicting Cytogenetic and Molecular Response in Newly Diagnosed Chronic Myeloid Leukemia-Chronic Phase Patients on Imatinib.

Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs. 273 patients with newly diagnosed CML were included in the study. They were treated with upfront imatinib. They were followed up for a median period of 3 years. Cytogenetic and Molecular response to the treatment were monitored regularly. Out of 273 patients, 174 patients (63 %) were having low EUTOS score and 99 (37 %) were having high EUTOS score. Patients with low, intermediate and high sokal scores were 237 (86.8 %), 28 (10.3 %) and 8 (2.9 %) respectively. 122 patients with low EUTOS score achieved CCyR within 18 months compared to 42 patients with high EUTOS score (p = 0.000).113 patients with low EUTOS score achieved MMR in 18 months compared to 33 patients with high EUTOS score (p = 0.000). 148, 14, 2 patients with low, intermediate and high Sokal score respectively have achieved CCyR in 18 months (p = 0.054). 133, 11, 2 patients with low intermediate and high sokal score respectively have achieved MMR in 18 months.(p = 0.06). EUTOS is better than Sokal score in predicting the outcome of patients of CML treated with imatinib.

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy.

CONTEXT: Carcinoma cervix is a leading cause of cancer in Indian females where 15%-60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. SETTINGS AND DESIGN: The study design was a retrospective analysis. MATERIALS AND METHODS: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). RESULTS: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. STATISTICAL ANALYSIS USED: It was carried out by SPSS software version 20. CONCLUSION: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research.

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.