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miRNAs are known to be aberrantly expressed in the serum, tissue, and Peripheral Blood Mononuclear Cells (PBMC) of cancer patients and could serve as potential noninvasive diagnostic markers for breast cancer. The aim of this study was to identify the differentially expressed miRNA using next-generation sequencing (NGS) from the paired PBMC samples from breast cancer patients and age-matched healthy individuals and explore their functional significance.In this study, PBMCs were employed for the detection of miRNAs by NGS in locally advanced breast cancer (LABC) women of South Indian origin who were divided into three age groups, (a) 40yrs-50yrs (b) 50yrs-60yrs and (c) 60yrs-70yrs, compared with age-matched control groups.Four miRNAs (hsa-miR-192-5p, hsa-miR-24-2-2p, hsa-miR-3609, and hsa-miR-664b-3p) were found to be differentially expressed among LABC patients compared with age matched healthy women of the South Indian population. While miR-24-2-5p, miR3609, and miR-664b-3p were down-regulated, miR-192-5p was up-regulated. Gene Ontology (GO) annotations implicated miRNA with signaling pathways in peripheral nerve synapses, glutamatergic synapse, and cell morphogenesis, all of which play a pivotal role in the manifestation of cancer.Four miRNAs- 3 (While miR-24-2-5p, miR3609, and miR-664b-3p) downregulated and one upregulated (miR-192-5p) were identified as potential biomarkers for patients with locally advanced breast cancer. These markers could be validated in studies with a larger sample size.

The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a randomized controlled trial to ascertain the benefit of a three-drug induction regimen. Patients aged 1–18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study’s primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives included comparing the composite complete remission (cCR) rates, overall survival (OS), and toxicities. The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The cCR rate in the DA and ADE arm were 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%, respectively (p = 0.74). There were no significant differences in toxicities between the regimens. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202).

Background: Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. Methodology: In this prospective, single-arm, open-label, phase 2 study, we included patients ≥18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for three days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. Results: 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17(94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after four months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were seven months and two months, respectively. Grade ≥3 adverse events were reported in 6 (33%) patients. Conclusion: The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide.

PURPOSE Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

Genetic factors could be attributed to the variability in docetaxel plasma levels and its subsequent therapeutic response. The objectives of this study were to assess the effect of ABCB1 gene polymorphisms [SNPs rs1045642 (C3435T) and rs1128503 (C1236T)] on docetaxel plasma levels and also to analyze the influence of docetaxel plasma levels on tumour response in the ethnically distinct South Indian population. 104 locally advanced breast cancer (LABC) patients on docetaxel-based neo‐adjuvant chemotherapy (NACT) were included. The plasma docetaxel levels were estimated using the validated reverse phase liquid chromatography with mass spectrometry (LC–MS/MS). DNA was extracted (phenol‐chloroform extraction method) and the real‐time PCR system using validated TaqMan® SNP genotyping assay method was used for genotyping. Tumour response was assessed by RECIST criteria based on the MRI images. Patients with “CT/TT” genotype of the SNP C1236T had a C0/Ct ratio of 1.6 times higher than those with “CC” genotype (13.5 ± 6.5 vs 8.3 ± 3.1, p = 0.002). Though not significant, patients with “CT/TT” genotype had greater initial plasma concentration (C0) and area under the plasma concentration–time curve (AUC0−t). Conversely, the SNP C3435T was not associated with the plasma docetaxel levels. Furthermore, the C0 and normalized C0 were found to be higher in tumour responders compared to non-responders (p

In this study, the role of change in tumor stiffness between pre- and post-two cycles of neoadjuvant chemotherapy (NACT) measured by Acoustic Radiation Force Impulse (ARFI) imaging for predicting the response to NACT in breast cancer was analyzed.Fifty-two adult women with biopsy-proven locally advanced breast cancer and early-stage breast cancer who received NACT followed by either modified radical mastectomy or breast conservation surgery were included in the study. Tumor stiffness represented by shear wave velocity (SWV) in meter per second by ARFI imaging was measured before and after two cycles of NACT. Participants were categorized into responders and nonresponders based on pathological response assessment from the postoperative specimen. The association of change in tumor stiffness between pre- and post-two cycles of NACT with final pathological response status was assessed.The mean change in SWV before and after completion of two cycles of NACT was 0.42 ± 0.16 and 0.17 ± 0.11 m/s in responders and nonresponders, respectively, and this difference was proven to be statistically significant (p 0.001) suggesting that tumors that exhibit a larger reduction in tumor stiffness, respond better. An SWV reduction cut-off of 0.295 m/s between baseline and post-two cycles of NACT was also arrived at, which can discriminate between responders and nonresponders with a sensitivity and specificity of 88% and 83%, respectively.Difference in tumor stiffness measured by ARFI imaging before and after two cycles of chemotherapy can be used as a reliable early predictor of response to chemotherapy in breast cancer.

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

Background The coronavirus disease 2019 (COVID‐19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery. Methods Weekly average of childhood cancer (≤18 years) patient registrations during pre‐lockdown period (January 1 to March 23, 2020) were compared with post‐lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post‐lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies. Results In 30 participating centers, 1146 patients with childhood cancer (797 pre‐lockdown period and 349 post‐lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre‐lockdown and post‐lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post‐lockdown was found significantly different by age (lesser older age, P = .010) and distance (lesser travel distance, P = .001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post‐lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations. Conclusions This multicenter study from India suggests that the COVID‐19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established., The coronavirus disease 2019 pandemic and the national lockdown in India since March 2020 led to delays in diagnosis and interruptions in the treatment of childhood cancer. This study reports a decline of 47.3% in the weekly average patient registration between pre‐lockdown and post‐lockdown, and 36.1% of patients experienced delays in 1 or more treatment modalities during the post‐lockdown period.

The covid-19 pandemic has impacted the management of non-covid-19 illnesses. Epithelial ovarian cancer (EOC) requires long-duration multidisciplinary treatment. Teleconsultation and shared care are suggested solutions to mitigate the consequences of the pandemic. However, these may be challenging to implement among patients who come from the lower economic strata. We report the disastrous impact of the pandemic on the care of EOC by comparing patients who were treated during the pandemic with those treated in the previous year. We collected the following data from newly diagnosed patients with EOC: time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients completing various components of therapy (surgery and chemotherapy). Patients treated between January 2019 and September 2019 (Group 1: Pre-covid) were compared with those treated between January 2020 and December 2020 (Group 2: During covid pandemic). A total of 82 patients were registered [Group 1: 43(51%) Group 2: 39(49)]. The median time from diagnosis to start of treatment was longer in group 2 when compared to group 1 [31(23–58) days versus 17(11–30) days (p = 0.03)]. The proportion of patients who had surgery in group 2 was lower in comparison to group 1 [33(77%) versus 21(54%) (p = 0.02)]. Proportion of patients who underwent neoadjuvant (NACT) and surgery were fewer in group 2 in comparison to group 1 [9(33%) versus 18(64%) p = 0.002]. Among patients planned for adjuvant chemotherapy, the median time from diagnosis to treatment was longer in group 2 [28(17–45) days, group 1 versus 49(26–78) days, group 2 (p = 0.04)]. The treatment of patients with EOC was adversely impacted due to the COVID-19 pandemic. There was a compromise in the proportion of patients completing planned therapy. Even among those who completed the treatment, there were considerable delays when compared with the pre-covid period. The impact of these compromises on the outcomes will be known with longer follow-up.

OBJECTIVES Epithelial ovarian cancer is one of the commonest gynecologic cancers and one with the highest mortality. This retrospective cohort study was done to identify predictors of outcomes in platinum-sensitive relapsed ovarian cancer patients (PS-ROC). METHODS Data regarding baseline characters, laboratory findings, therapeutic details and survival outcomes was obtained from the medical records of PS-ROC patients presented between January 2015 and December 2019. Prognostic score was constructed using factors which were significant on multivariate analysis to predict survival outcomes. RESULTS A total of 71 (PS-ROC) patients were included in the study with a median age of 50 years. Relapse treatment was either chemotherapy alone (n=53, 75%) or chemotherapy plus surgery (n=18, 25%). The estimated progression-free survival (PFS) and overall survival were 10 and 29 months, respectively. The overall response rate after treatment of relapse was 59%. Prognostic score was created with the 3 factors (each scoring 1 point) which were predictive of PFS (higher lymphocyte-monocyte ratio, longer platinum-free interval and secondary cytoreduction). Patients with low score (0,1) had better PFS than those with higher score (2,3) (13 vs. 7 mo [P=0.0001]). CONCLUSIONS A composite prognostic score could predict outcomes in PS-ROC and potentially identify a subgroup with very poor prognosis. Future studies with a greater number of patients are needed to validate these findings. This information could help tailor more intense therapies to the high-risk patients and attempt to improve outcomes and serve as stratification factors for prospective trials.

Purpose: To study the late toxicities of treatment and its impact on Breast cancer survivors among Indian patients. Materials and Methods: Our study recruited 152 curatively treated non metastatic carcinoma breast patients. The baseline demographic details, disease related and treatment related information were collected. The late effects included breast cancer related lymphedema, shoulder dysfunction, treatment induced bone loss, hypothyroidism, cardiac dysfunction, and chemotherapy induced cognitive dysfunction and Quality of life. Results: The median age was 47 years (range 27 -72 years). The cumulative frequency of BCRL and shoulder dysfunction was 31.57% and 34.86% respectively. The improvement in BCRL with corrective intervention was not statistically significant. The BCRL was significantly associated with shoulder dysfunction. The frequency of loss of bone mineral density was 38.15%. There was statistically significant improvement in bone mineral density with interventions. The cumulative rate of hypothyroidism and cardiac dysfunction was 14.47 % and 2.17% respectively which improved after corrective therapy. We did not find any delayed cognitive dysfunction. There was improvement in global health, physical function, role function, fatigue, Nausea, vomiting, pain scores, insomnia, Loss of appetite, diarrhea and arm symptoms over time with intervention. Conclusion: Our study has shown that nearly half of the survivors were suffering from at least one of the late effects. The intervention helped in improving the loss of bone mineral density, hypothyroidism, cardiac dysfunction and quality of life in Breast cancer survivors.

Anemia is a common finding and important cause of morbidity in patients with acute lymphoblastic leukemia (ALL) at diagnosis or during the course of its protracted treatment. We studied profile of anemia in ALL patients on maintenance therapy and evaluated specific micronutrients as cause of this anemia.ALL patients who were on maintenance therapy and had grade ≥ 2 anemia were recruited for the study. Serum iron studies, folate, and vitamin B12 were done to identify micronutrient deficiency and to initiate supplementation with specific components if found to be deficient. Toxicities, improvement of anemia, micronutrient levels, and disease outcome were studied after 3 months.From March 2015 to September 2016, 105 ALL patients were found to be on maintenance fulfilling the inclusion criteria. Overall, the proportion of anemia was 80%(N = 84). Majority had normocytic normochromic anemia (71%). Macrocytic anemia was seen in 18% and microcytic hypochromic in 9.5%. In patients with anemia of grade ≥ 2 (N = 84), 38 patients (45%) had biochemical deficiency of serum folate, and 7 (8%) had vitamin B12 deficiency. No biochemical evidence of iron deficiency was found. Supplementation of deficient micronutrients improved anemia: mean hemoglobin significantly increased from 8.06 ± 1.63 to 10.78 ± 1.53 (p 0.001) at 3 months; and reduced treatment toxicities, mean number of febrile neutropenia episodes (p = 0.007), and treatment interruptions of 2 weeks (p = 0.002) were lowered. Patients with anemia had significantly more relapses (N = 14,64%) compared to patients without anemia (N = 8,36%), (p = 0.040).Timely identification and correction of micronutrient deficiencies causing anemia in ALL patients on maintenance can enhance treatment outcomes.

Extraosseous Ewing's Sarcoma (EES) is a high grade rare malignancy from Ewing's family tumors (EFTs) occurring in soft tissues. Diagnosis of EES relies on a constellation of features, including round cell morphology, characteristic immunohistochemistry (such as CD99, FLI-1 and NKX2.2 positivity), and pathognomic molecular abnormalities of t(11;22)(q24;q12). Multimodality treatment has improved the prognosis and clinical outcome in EFTs. Due to its rarity, the current recommendation to treat EES is based on Skeletal Ewing's Sarcoma (SES) guidelines. However, achieving clear surgical margins in the Head and Neck region is often challenging due to complex anatomy and close proximity to critical structures, placing patients at risk of loco-regional recurrence in the absence of adjuvant therapy. The literature on head and neck EES is scarce, consisting of a few retrospective case series and case reports. Herein, we describe the characteristic clinico-pathological features and treatment of three EES patients with primaries from Parotid, Nasal cavity/ Nasopharynx and Oropharynx, with a comprehensive review of the literature. Keywords: Ewing's Family of tumors, Extraosseous Ewing's sarcoma of head and neck.

Hematopoietic stem-cell transplantation (HSCT) is a life-saving procedure often performed to cure relapsed and difficult-to-treat malignancies. Only a handful of centers in India were initially involved in the delivery of these services. However, in the last decade, more than 100 centers in the private and public domain have started offering transplant services in the country. Moreover, there are funding options, which has opened up this expensive treatment options for economically backward patients. Costs apart, there are multiple social, familial, and emotional challenges faced by these patients. A multidisciplinary support team involving social workers, psychologists, and transplant nurses, besides the treating hematologist/oncologist, is required for the optimum care of these patients. These challenges, in the Indian context, are often unique. Unfortunately, there is limited information and resource available to guide counseling of patients planned for HSCT in India. We conducted a workshop at our center where a panel of experts with experience in dealing with patients undergoing HSCT discussed issues faced by them. These discussions constitute a valuable resource for counseling patients planned for HSCT. They were transcribed by a postgraduate doctor and are summarised here in a case-based format.

Breast cancer (BC) is one of the most common malignancies worldwide. Although the burden and mechanisms of endocrine therapy-related bone loss are known, the evidence is scanty regarding the impact of cytotoxic chemotherapy on bone health. We have attempted to summarize the effect of cytotoxic chemotherapy on bone health in BC patients. A comprehensive literature search was performed via MEDLINE and Cochrane library databases to evaluate the effect of chemotherapy on bone health among women with BC. We included articles related to skeletal-related events, bone mineral density, bone turnover markers, osteoporosis-specific quality of life, bisphosphonate, and other bone-directed therapy. We excluded articles that included patients with metastatic breast cancer and patients receiving hormonal therapy. Bone microenvironment in cancer is directly or indirectly influenced by clinical, hormonal, nutritional, and treatment factors. Calcitonin, parathyroid hormone, calcitriol, and estrogen are the major hormonal regulators. Bone turnover markers, namely bone formation and resorption markers, have been used to predict bone loss, fracture risk, and monitoring treatment response. Chemotherapeutic drugs such as anthracyclines and taxanes synergistically affect BMD and quality of life. Calcium, vitamin D, bisphosphonates, and denosumab are supplemented to prevent excess bone resorption. Bone-targeted anti-resorptive agents have been studied as potential anticancer agents in the adjuvant treatment of breast cancer. This review summarizes the negative effect of chemotherapy on bone health of BC patients and the importance of preventing or treating bone loss.

Triple-negative subtype is an aggressive breast cancer with inferior survival. Pathological complete remission (pCR) is a good surrogate endpoint for survival among patients receiving neoadjuvant chemotherapy (NACT). We attempted to validate the clinical pathological score (CPS) with a modified risk grouping among Triple-negative breast cancer (TNBC) patients receiving NACT at our center.Data of patients with TNBC who underwent NACT between January 2014 to July 2017 were retrospectively analyzed. The composite CPS score included cTN stage and y pTN stage and ranged from 0 to 4. This was calculated using an available online software developed by MD Anderson Center. The score obtained from the calculator was used to develop a risk grouping into low risk (0, 1) and high risk (2, 3, 4). Invasive disease-free survival (iDFS) and locoregional recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method.Seventy-eight patients with TNBC (median age: 45 [24-75]) had received NACT (anthracyclines and taxanes). Early and locally advanced breast cancer constituted 17 (21.8%) and 61 (78.2%), respectively, and 22 (28.2%) achieved pCR. After a median follow-up of 25 months (5-62), 3-year iDFS and OS were 59% and 81%, respectively, for the entire population. The 3-year iDFS in low-risk (n = 18) and high-risk (n = 60) patients was 85% and 51%, respectively (P = 0.03). The 3-year LRFS in low risk and high risk was 93% versus 58% (P = 0.03). The 3-year OS in the low and high risk was 93% and 77%, respectively (P = 0.24, NS).Our study supports the use of the modified neoadjuvant clinicopathological score as a prognostic marker in patients with nonmetastatic triple-negative breast cancer. This needs to be validated in a larger subset of patients.

Digestive tract cancer patients treated with oxaliplatin are often associated with the development of peripheral neuropathy. The aim of the present study is to identify the influence of single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, cell cycle control, detoxification or excretion pathways with the development of oxaliplatin-induced acute peripheral neuropathy (acute OXAIPN) and its severity among digestive tract cancer patients treated with oxaliplatin-based chemotherapy. A total of 228 digestive tract cancer patients undergoing with the oxaliplatin-based chemotherapy between November 2014 and December 2016 were included in the current study. Genomic DNA was extracted from peripheral blood by standard phenol–chloroform method. Genotyping of five SNPs in four genes [GSTP1 (rs1965), ABCG2 (rs3114018), CCNH (rs2230641, rs3093816), AGXT (rs4426527)] was carried out by Real-Time TaqMan SNP genotyping assay. We found that the two genetic variants rs2230641 and rs3093816 in cyclin H (CCNH) gene were significantly associated with both the incidence and severity of acute OXAIPN. For CCNH-rs2230641 (AA vs AG+GG; dominant model) Incidence: OR 2.62, 95% CI 1.44–4.75, p = 0.001, severity; OR 4.64, 95% CI 1.58–13.62, p = 0.002. For CCNH-rs3093816 (AA vs AG+GG; dominant model); incidence: OR 3.43, 95% CI 1.57–7.50, p = 0.001; severity: OR 2.36, 95% CI 1.05–5.30, p = 0.033. The results of the present study found significant association between CCNH polymorphisms and acute OXAIPN development. However, further studies are warranted from independent groups to validate our study results.

Langerhans' cell histiocytosis is an uncommon disease in children with varied clinical presentation. Multisystem form of this disorder usually affects organs like the bones, skin, liver, spleen, lungs, and the central nervous system. We describe here the clinical details of a 2-year-old girl with involvement of unusual sites like the parotid glands and the nails. This child also had multiple cystic lesions in the liver leading to a misdiagnosis of Caroli's disease. Knowledge about the uncommon manifestations of this rare disorder helps in early diagnosis and treatment.

What is known and objective Variable response to docetaxel-based neo-adjuvant chemotherapy (NACT) in breast cancer patients had been reported. Genetic polymorphisms in the ABCB1 gene coding for the efflux transporter MDR1 (P-glycoprotein, P-gp) could result in altered tumour response. Hence, this study was proposed to assess the effect of single nucleotide polymorphisms (SNPs) of ABCB1 gene on tumour response in locally advanced breast cancer patients (LABC) of South India who have a distinct genetic makeup. Methods Out of 162 LABC patients recruited, 129 patients were included for the final analysis. DNA was extracted by "phenol-chloroform extraction method" from the WBCs, and genotyping for SNPs rs1045642 (C3435T) and rs1128503 (C1236T) in ABCB1 gene was performed with real-time PCR system using validated TaqMan® SNP genotyping assay method. Tumour response was assessed by RECIST criteria based on the MRIs taken before and after completion of four cycles of docetaxel therapy. Results and discussion A total of 102 (79.1%) patients were found to be responders and 27 (20.9%) patients were found to be non-responders to docetaxel therapy. Patients with "CT/TT" genotypes (response rate: 83.3%) of ABCB1 (C1236T) gene showed better tumour response than those with "CC" genotype (response rate: 16.6%) [OR = 2.94 (CI: 1.15-7.52); P = 0.03]. However, on performing binary logistic regression, neither the studied SNPs nor the non-genetic factors like age, BMI, postmenopausal status, laterality of the tumour, ER status, PR status and Her-2/neu status were found to be associated with tumour response to docetaxel (P > 0.05). What is new and conclusion The tumour response to docetaxel was significantly influenced by the SNP C1236T of ABCB1 gene coding for the P-gp. However, when adjusted for other non-genetic factors, neither of the ABCB1 variants were found to be associated with tumour response to docetaxel-based NACT in LABC patients of South India.

BACKGROUND: Maintenance treatment of patients with advanced nonsmall cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of this study was to investigate the efficacy, safety, and tolerability of the epidermal growth factor receptor (EGFR)–tyrosine-kinase inhibitor, i.e., gefitinib in the maintenance setting irrespective of EGFR status. METHODS: Patients aged 18 years or older of Indian origin, who had a life expectancy of >12 weeks with histologically or cytologically confirmed Stage IV NSCLC, the WHO performance status of 0–2, and who had completed four to six cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects were included in the study. The primary endpoint of the study was progression-free survival in the intention-to-treat population. RESULTS: Twenty-five patients with a median age of 55 years (40–68) were included in the study. The median progression-free survival (PFS) for the entire group was 8 months (95% confidence interval [CI] =1.45–14.54) had not reached for EGFR-positive patient, but in the EGFR negative cohort, the PFS was 4.98 months (hazard ratio = 0.092, 95% CI = 3.4–6.5, P = 0.01). The median overall survival (OS) of the study group was 15 months (95% CI = 3.7–26.4), all patients with EGFR positive were alive (100% survival). The median OS for EGFR negative group was about 6.3 months. The major toxicity observed was rash/acne in 15 patients, pruritus in 7 patients, and one patient had Grade 4 pneumonitis. CONCLUSION: Gefitinib maintenance is safe, well-tolerated therapy, produces significant PFS and OS benefit in EGFR mutation-positive patient. It is definitely not a choice for EGFR negative group. In EGFR unknown group, the role of maintenance still needs to be explored.

BACKGROUND: Gemcitabine and carboplatin combination is widely used as one of the first-line chemotherapeutic regimens in patients with metastatic nonsmall cell lung cancer patients. METHODOLOGY: A total of 112 patients with metastatic disease were recruited. They were on standard 21-day gemcitabine 1.2 g/m 2 and carboplatin AUC 5 dosing schedule. Each patient received at least four cycles and a maximum of 6 cycles of treatment. The patients were followed up, and the demographic, efficacy and toxicity profiles were analyzed. RESULT: The mean age was 53.81±9.85 with 71 male and 41 female patients. Response assessment was done in 82 patients, and the objective response rate was found to be 47.6% with 39 partial responders, 20 patients with stable disease and 23 patients with progressive disease. The median overall survival was 12 months (95% CI 9.89-14.11). We found anemia (62.5%) to be more prominent than the other toxicities followed by thrombocytopenia and vomiting (31.3%). The nonhematological toxicities were minimal and manageable. CONCLUSION: Treatment with gemcitabine and carboplatin is efficacious with manageable toxicity profile in the real world non-clinical trial setting.

Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN. One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents. Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%). Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Background Intravenous high-dose melphalan has a short half-life, and application of this single drug in MM transplant favors the use of stem cells without cryopreservation, for wider use in general and in resource-limited settings in particular. Patients and Methods Ninety-two patients with MM were given high-dose melphalan and rescued with granulocyte colony stimulating factor (G-CSF) mobilized noncryopreserved autologous PBSC, in our hospital during the past 18 years. Stem cells were mobilized with 4 days of G-CSF, harvested (median CD34 dose, 2.9 × 10 6 /kg) and then stored at 4°C in a refrigerator for a median of 2 days (range, 1-5 days) before reinfusion. Results Median time to neutrophil (> 500/mm 3 ) and platelet (> 20,000/mm 3 ) engraftment were 10 and 14 days respectively. There was no graft failure. Mucositis grade 3/4 was seen in 66 patients (72%). Transplant-related mortality at 100 days was 3.2%. The overall response to transplant was 88% and improvement compared with pretransplant status was seen in 48%. The median overall survival (OS) and progression-free survival (PFS) were 61.7 months and 35.4 months respectively; independent predictors of survival were Eastern Cooperative Oncology Group Performance Status and hemoglobin for OS and chemosensitive disease and remission status after transplant for PFS. Conclusion We conclude that high-dose chemotherapy and autologous transplant with noncryopreserved PBSC is a simple, effective, and safe method for MM with equivalent results, and that cryopreservation is not necessary. It reduces the cost of transplant and avoids dimethyl sulfoxide toxicity.

The aim of the study was to assess and compare the clinical and pathological response and the toxicity profile between neoadjuvant chemotherapy FEC followed by docetaxel versus AC followed by docetaxel in locally advanced breast cancer patients. Between June 2013 and June 2014, 148 patients diagnosed with LABC were randomized into two groups with 74 in each group. Group 1 received AC (adriamycin 60 mg/m(2), cyclophosphamide 600 mg/m(2)) followed by docetaxel 100 mg/m(2) with primary GCSF prophylaxis and group 2 received FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) followed by docetaxel 75 mg/m(2). MRM/BCS was performed for all patients after NACT and assessed for pathological response. Toxicity profile was assessed according to CTCAE version 4. All baseline parameters were equally matched between the two regimens. 90 % of patients completed NACT and underwent surgery. pCR rates were 31 % in group 1 and 34 % in group 2 without any difference. Any grade of hand-foot syndrome was significantly high in group 1 as compared to group 2. Grade 3 and grade 4 neutropenia and febrile neutropenia were significantly high in group 1 as compared to group 2. Median follow-up was 13.7 months (range, 2.9-25 months). There was no difference in the 2-year PFS between group 1 and group 2 (70.9 vs. 73.8 %, respectively) and OS (87.8 vs. 91.8 %, respectively) in our study population. Chemotherapy with FEC followed by docetaxel can be considered as an optimal neoadjuvant regimen in LABC as compared to AC followed by docetaxel.

A novel biomarker, CD68, which marks tumor-associated macrophages (TAMs) in the microenvironment, has recently been reported to affect the prognosis of Hodgkin lymphoma (HL). We aimed to evaluate its role in our patient cohort (n = 100) by utilizing a routine immunohistochemistry method on whole tissue sections and a semiquantitative method for CD68 scoring. Clinical data were taken from medical records. Correlation with baseline characteristics, attainment of complete remission (CR), progression-free survival (PFS) and disease-specific survival (DSS) was done by categorical analysis using different cut-offs of CD68 score and also by taking absolute CD68 score as a continuous variable. There was no significant association between levels of CD68 expression and baseline characteristics or CR after primary therapy. CD68 score (neither categorical nor absolute continuous values) also did not predict for any difference in PFS or DSS. We conclude that CD68 TAM marker does not have prognostic value in HL.