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Autologous stem cell transplant (ASCT) is a standard therapy for transplant eligible patients of multiple myeloma (MM). To evaluate impact of time to transplant on subsequent outcomes, we analyzed data on consecutive MM patients who received novel agents-based induction prior to transplant.Between 2006 and 2019, 363 MM patients underwent ASCT. Patients' median age was 52 years, ranging from 20 to 72 years, 233 (64.2%) were males. Median interval from diagnosis to transplant was 11.5 months (range, 4-67.5); 201 (55.4%) patients underwent ASCT within 12 months (early) and 162 (44.6%) beyond 12 months since diagnosis (delayed ASCT). Primary objective was progression-free survival. Secondary objectives were-response rate to transplant, overall survival (OS), and transplant-related mortality (TRM).Post-ASCT complete response (CR) (77.1% vs. 64.8%; P.025) and CR+ very good partial response rate (89% vs. 81.5%; P.03) was higher for early ASCT cohort. Engraftment characteristics, regimen-related toxicities, and day +100 TRM (3.5% vs 3.7%; P = .564) were similar in 2 cohorts. Median OS for early versus late cohort from date of diagnosis is 127.0 (95% CI, 98.9-155.1) versus 104.5 months (95% CI, 79.3-129.6; P = .356) and from date of transplant is 119.0 (95% CI, 93.4-144.6) versus 89.5 months (95% CI, 57.4-121.6), P.02. Median PFS is better for early transplant cohort; 69.5 (95% CI, 56.7-82.3) versus 50.0 months (95% CI, 35.6-64.4), P.05, respectively.Early transplant for myeloma is associated with higher response rate and better progression-free survival.

Introduction Ovarian cancer is the third most common cancer among Indian women. The data on the hereditary predisposition of these cancers and the clinical outcomes of those with pathogenic mutations is meager in India. Objective The aim of the current study was to analyze the germline-genetic profile, clinicopathological characteristics, and outcomes of patients with ovarian cancer who were referred for genetic counseling at our Institute. Materials and Methods It was a cross-sectional observational study. Patients with histological diagnosis of carcinoma ovary at our institute who were referred for genetic counseling from July 2017 to June 2020 were included in the study. All patients underwent pretest counseling. Most patients underwent multigene panel testing with reflex multiplication ligation-dependent probe amplification for large genomic rearrangements, while some received testing for BRCA1 and BRCA2 only. The variants were classified as pathogenic or benign based on American College of Medical Genetics (ACMG) guidelines. Data regarding the demographic profile, clinical characteristics, histopathological findings, family history, treatment received, and outcomes were extracted from the medical record system files. Results One hundred and one patients were referred to the genetic clinic and underwent genetic counseling. All patients were advised for genetic testing; however, only 72 (71%) underwent testing. A multigene panel testing was done in 51 (70%) patients, and only BRCA1 and BRCA2 genes were tested in 21 (30%). Among the 72 patients who underwent a genetic test, the median age was 47 years (range, 28–82). The most common histopathology was serous (90%), while 85% were diagnosed having stage 3 and 4 ovarian cancer. A pathogenic/likely pathogenic (P/LP) BRCA or non-BRCA mutation was detected in 32 (44%) patients. Six patients (8%) had a variant of unknown significance (VUS). Among P/LP mutations, 85% were in the BRCA gene (75% in BRCA1 and 10% in BRCA2), while 15% were in non-BRCA gene mutations (RAD51, PALB2, MER11, HMMR). Disease-free survival and overall survival were not different in mutation-positive and mutation-negative cohorts. Conclusions We report 44% P/LP mutations in this selected cohort of patients with carcinoma ovaries. BRCA mutations constituted 85% of all the mutations, while 15% of mutations were in non-BRCA genes.

Introduction Hereditary breast and ovarian cancer (HBOC) syndrome affects a significant proportion of our breast and ovarian cancer patients. Mutations in genes, for example, BRCA1 and 2, confer a high risk of acquiring certain malignancies, including breast cancer in both men and women, and ovarian cancer in women. Mutation carriers provide a unique opportunity for healthcare professionals to intensively screen and detect malignancy at an early and curable stage. But, patient awareness and acceptance are the keys to the success of these strategies. Objective There is a need to assess the awareness of the patients in this field as the patients come from varied backgrounds, and differ in their socioeconomic profiles, educational backdrop, and cultures. In this study, done prior to establishing our cancer genetics clinic, we evaluated the knowledge and attitude toward HBOC in patients with breast cancer and ovarian cancer. Materials and Methods This cross-sectional observational study was conducted on patients registered in IRCH-AIIMS, who has a diagnosis of breast cancer or ovarian cancer using a self-administered questionnaire based on knowledge and attitude. The sample population included 84 women aged between 25 and 80 years. A binary response was given to knowledge questions, whereas a categorical response was given to attitude questions. The overall data was computed using STATA v13 software. Results According to the findings of the study, 39.3% (5.11/13) of the patients were aware of hereditary cancer. Knowledge among the targeted population was poor, but 72.1% (37.5/52) of the population had a neutral attitude toward learning more about hereditary cancer tests. Only 23/84 (27%) people had heard of genetic counseling. Seventy of eighty-four (83%) patients agreed that they would opt for a genetic test if indicated. While 60/84 (72%) of the population wanted to interact with a counselor over a telephonic call, only 41/84 (49%) wanted to interact in person. Conclusion We concluded from the study that breast and ovarian cancer patients in our clinic have little understanding of HBOC syndrome but have a neutral attitude toward learning more about it.

Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.

GRP78 overexpression in myeloma cells has been associated with bortezomib resistance in multiple myeloma (MM). However, serum GRP78 as a maker of bortezomib-based treatment response remains unexplored. The objective of the study was to evaluate serum GRP78 levels in MM patients who underwent a bortezomib-based induction regimen. This cross-sectional study included adult MM patients (n=30) who completed at least four cycles of bortezomib-based induction therapy. Healthy volunteers (n=30) and newly diagnosed MM patients (n=19) were also recruited to identify the disease-associated change in GRP78 levels. Serum GRP78 was estimated by ELISA. Surface and intracellular expression of GRP78 in bone marrow plasma cells was evaluated in ten MM patients by flow cytometry. Among 30 MM patients [median (range): 52 (38-68) years; 20 males] who completed at least four cycles of bortezomib-based induction therapy, 20 were responders and 10 were non-responders. Serum GRP78 levels were not significantly different between responders [median (IQR): 5.2 (3.1, 8.0) μg/ml] and non-responders [median (IQR): 4.3 (0.1, 7.1) μg/ml] (p=0.4). Although non-significant (p=0.3), median serum GRP78 was higher in newly diagnosed patients when compared to healthy volunteers. Bone marrow plasma cells ranged from 0.2 to 57.8% in the analyzed samples. Intracellular GRP78 expression in bone marrow plasma cells was higher (1.6 to 5 times) when compared to surface expression. To conclude, serum GRP78 levels vary widely in different MM patient groups but did not correlate with response to a bortezomib-based induction regimen.

PURPOSE Tyrosine kinase inhibitors such as sunitinib and pazopanib are the mainstay of treatment of metastatic renal cell carcinoma (mRCC) in India. However, pembrolizumab and nivolumab have shown significant improvement in the median progression-free survival and overall survival among patients with mRCC. In this study, we aimed to determine the cost-effectiveness of the first-line treatment options for the patients with mRCC in India. METHODS A Markov state-transition model was used to measure the lifetime costs and health outcomes associated with sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab among patients with first-line mRCC. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost-effectiveness using a willingness to pay threshold of one-time per capita gross-domestic product of India. The parameter uncertainty was analyzed using the probabilistic sensitivity analysis. RESULTS We estimated the total lifetime cost per patient of ₹ 0.27 million ($3,706 US dollars [USD]), ₹ 0.35 million ($4,716 USD), ₹ 9.7 million ($131,858 USD), and ₹ 6.7 million ($90,481 USD) for the sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab arms, respectively. Similarly, the mean QALYs lived per patient were 1.91, 1.86, 2.75, and 1.97, respectively. Sunitinib incurs an average cost of ₹ 143,269 ($1,939 USD) per QALY lived. Therefore, sunitinib at current reimbursement rates (₹ 10,000 per cycle) has a 94.6% probability of being cost-effective at a willingness to pay threshold of 1-time per capita gross-domestic product (₹ 168,300) in the Indian context. CONCLUSION Our findings support the current inclusion of sunitinib under India's publicly financed health insurance scheme.

Background Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker. Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival. Results Of 32 cases, most (n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly (n = 25, 81.2%) or dose-dense weekly (n = 6, 18.8%) regimen. The majority (n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59–66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival (p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05). Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.

Background: Routinely, patient’s planning scans are acquired after administration of iodinized contrast media but they will be treated in the absence of that. Similarly, high energy photons have a better penetrating power, while low energy photons will result in tighter dose distribution and negligible neutron contamination. The aim of the study was to investigate a suitable photon beam energy in the presence of intravenous contrast medium. Materials and methods: An indigenously made original-contrast (OC) phantom was mentioned as virtual-contrast (VC) and virtual-without-contrast (VWC) phantom were generated by assigning the Hounsfield Units (HU) to different structures. Intensity-modulated (IMRT) and volumetric-modulated-arc (VMAT) plans were generated as per criteria of the TG-119 protocol. Results: It was observed that the maximum dose to the spinal cord was better with 6 mega-voltage (MV) in IMRT. The coverage of Prostate PTV (PR PTV) was similar with all the photon energies and was comparable with TG-119, except for original-contrast (OC) phantom using the VMAT technique. Homogeneity-index (HI) was comparatively better for VMAT plans. Conclusion: The contrast CT images lower the dose to targets. IMRT or VMAT plans, generated on such CT images will be delivered with higher doses than evaluated. However, the overdose remains non-significant

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (

The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner.A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were DDRadiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (DVMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Background Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. Patients and methods Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. Results Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has ‘not reached’ in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in ‘symptom scales’ in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p Conclusion Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. Trial registration CTRI/2017/10/010219.

Background: Cancer is characterized by uncontrolled cell division in the human body damaging normal tissues. There are almost a hundred types of cancers studied to date that are conventionally treated with chemotherapy, radiation therapy, and surgery. Conventional methods have drawbacks like non-specific distribution of drugs, low concentration of drugs in tumors, and adverse effects like cardiotoxicity. Therefore, inorganic nanoparticles are explored nowadays to achieve better results in cancer treatment. Objective: The objective of this review paper was to summarize the role of inorganic nanoparticles in cancer treatment by revealing their preclinical status and patents. Methods: Literature survey for the present work was conducted by exploring various search engines like PubMed, Google Scholar, and Google patents. Results: Inorganic nanoparticles come under the advanced category of nanomedicine explored in cancer therapeutics. The structural properties of inorganic nanoparticles make them excellent candidates for targeting, imaging, and eradication of cancer cells. Besides this, they also show high biocompatibility and minimum systemic toxicity. Conclusion: This review paper concludes that inorganic nanoparticles may be better alternatives to conventional approaches for the treatment of cancer. However, their presence in global pharmaceutical markets will be governed by the development of novel scale-up techniques and clinical evaluation.

PURPOSE Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Background: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin. Methods: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance. Results: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73–7.3) and 5.03 months (95% CI 2.63–7.43) in each arm, respectively (HR 1.13, 95% CI 0.81–1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5–18.73) and 11.3 (95% CI 8.3–19.7; HR 1.19, 95% CI 0.8–1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm. Conclusion: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.

Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.

CD123 is overexpressed in many hematologic malignancies and found to be useful in characterizing leukemic blasts of both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 has been recently found to be a marker of leukemic stem cells, and its utility to measure residual disease and potential role in disease relapse is under evaluation.Herein, we have evaluated the expression of CD123 in 757 samples of acute leukemia including 479 treatment-naive and 278 follow-up samples and compared with post-induction morphologic complete remission and measurable residual disease (MRD) status. Multiparametric flow cytometry was used for assessment of CD123 expression and immunophenotypic characterization of leukemic blasts at diagnostic and MRD assessment time points.Using variable cutoffs of 5%, 10%, and 20% to define a case as CD123-positive, expression of CD123 was observed in 75.6%, 66.2%, and 50% of AML and 88.6%, 81.8%, and 75% of B-ALL, respectively. Of 11 patients, 7 (63.63%) had mixed phenotype acute leukemia, but none of the 12 patients with T-acute lymphoblastic leukemia showed positivity for CD123. CD123 expression at diagnosis was associated with post-induction MRD-positive status in both B-ALL (P .001) and AML (P = .001). We also evaluated the utility of CD123 as a leukemia-associated aberrant immunophenotype and found it to be useful in both patients with AML (baseline, 50.6%; follow-up, 53%) and B-ALL (baseline, 75%; follow-up, 73.07%).In conclusion, CD123 may be considered as a cardinal marker for residual disease assessment and response evaluation in AML and B-ALL.

AIM: To investigate the impact of Acuros XB (AXB) algorithm in the deep-inspiration breath-hold (DIBH) technique used for treatment of left sided breast cancer. BACKGROUND: AXB may estimate better lung toxicities and treatment outcome in DIBH. MATERIALS AND METHODS: Treatment plans were computed using the field-in-field technique for a 6 MV beam in two respiratory phases - free breathing (FB) and DIBH. The AXB-calculations were performed under identical beam setup and the same numbers of monitor units as used for AAA-calculation. RESULTS: Mean Hounsfield units (HU), mass density (g/cc) and relative electron density were -782.1 ± 24.8 and -883.5 ± 24.9; 0.196 ± 0.025 and 0.083 ± 0.032; 0.218 ± 0.025 and 0.117 ± 0.025 for the lung in the FB and DIBH respiratory phase, respectively. For a similar target coverage (p > 0.05) in the DIBH respiratory phase between the AXB and AAA algorithm, there was a slight increase in organ at risk (OAR) dose for AXB in comparison to AAA, except for mean dose to the ipsilateral lung. AAA predicts higher mean dose to the ipsilateral lung and lesser V(20Gy) for the ipsilateral and common lung in comparison to AXB. The differences in mean dose to the ipsilateral lung were 0.87 ± 2.66 % (p > 0.05) in FB, and 1.01 ± 1.07% (p

Insulin-signalling is an important pathway in multiple cellular functions and organismal ageing across the taxa. A strong association of insulin-signalling with Parkinson’s disease (PD) has been proposed but the exact nature of molecular events and genetic associations are yet to be understood. We employed transgenic C. elegans strain harboring human α-synuclein::YFP transgene, towards studying the aggregation pattern of α-synuclein, a PD-associated endpoint, under human insulin (Huminsulin®) treatment and DAF-16/DAF-2 knockdown conditions, independently and in combination. The aggregation was increased when DAF-16 was knocked-down independently or alongwith a co-treatment of Human insulin (HumINS) and decreased when DAF-2 was knocked-down independently or alongwith a co-treatment of HumINS; whereas HumINS treatment per se, reduced the aggregation. Our results depicted that HumINS decreases α-synuclein aggregation via DAF-2/DAF-16 pathway by acting as an antagonist for DAF-2 receptor. Knockdown of reported DAF-2 agonist (INS-6) and antagonists (INS-17 and INS-18) also resulted in a similar effect on α-synuclein aggregation. Further by utilizing bioinformatics tools, we compared the differences between the binding sites of probable agonists and antagonists on DAF-2 including HumINS. Our results suggest that HumINS treatment and DAF-16 expression play a protective role against α-synuclein aggregation and its associated effects.

Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080–3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224–0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.

Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials. Since then CCRT has been the standard treatment approach; this has resulted in 5-year overall survival rate of 66% and disease-free survival (DFS) of 58%. About 30% to 40% of patients with locally advanced cervical cancer continue to have treatment failure. Also, some patients experience early and late side effects of treatment with negative impact on quality of life. To improve the outcome further - recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients. For patients with early stage disease (IA2-IIA), short course chemotherapy prior to surgery is associated with improved outcome in many studies. Bevacizumab- an inhibitor of vascular endothelial growth factor - is associated with improved survival. More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.

To validate the AcurosA Clinac-iX (2300CD) linear accelerator and Eclipse TPS (Varian Medical System, Inc., Palo Alto, USA) was used for commissioning of AXB algorithm using a 6 megavolts photon beam. Percentage depth dose (PDD) and profiles for field size 2 cm × 2 cm, 4 cm × 4 cm, 6 cm × 6 cm, 10 cm × 10 cm, 20 cm × 20 cm, 30 cm × 30 cm to 40 cm × 40 cm were taken. AXB calculated PDDs and profiles were evaluated against the measured and analytical anisotropic algorithm (AAA)-calculated PDDs and profiles. Test sites recommended by American Association of Physicists in Medicine task group (AAPM TG)-119 recommendation were used for RA planning and delivery verification using AXB algorithm.Dosimetric analysis of AXB calculated data showed that difference between calculated and measured data for PDD curves were maximum1% beyond the depth of dose maximum and computed profiles in central region matches with maximum1% for all considered field sizes. Ion-chamber measurements showed that the average confidence limit (CLs) was 0.034 and 0.020 in high-gradient and 0.047 and 0.042 in low-gradient regions, respectively, for AAA and AXB calculated RA plans. Portal measurements show the average CLs were 2.48 and 2.58 for AAA and AXB-calculated RA plans, with gamma passing criteria of 3%/3 mm.AXB shows excellent agreement with measurements and AAA calculated data. The CLs were consistent with the baseline values published by TG-119. AXB algorithm has the potential to perform photon dose calculation with comparable fast calculation speed without negotiating the accuracy. AAPM TG-119 was successfully implemented to access the proper configuration of AXB algorithm following the TPS upgrade.

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p < 0.001), age >60 years (p = 0.001), bulky disease (p < 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p < 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

One fifth of patients with epithelial ovarian cancers (EOC) present at an early stage (FIGO stage III). However, there is scarcity of literature on the outcomes and its predictors. The aim of the study was to assess relapse free survival (RFS), overall survival (OS) and its predictors in early stage EOC.In this retrospectively study, we included all patients with early-stage EOC diagnosed between January 2010 and December 2018. Patients with synchronous malignancies were excluded. Clinical profile, clinico-pathological characteristics and treatment details were recorded. Patient underwent initial surgery followed by adjuvant chemotherapy in high-risk disease. Patients with stage IC, or stage II or clear cell histology or high-grade histology irrespective of stage/histological subtype were defined as high-risk disease. Fertility sparing surgery (FSS) [unilateral salpingo-oopherectomy with complete surgical staging] was performed in patient willing to preserve fertility. Primary objective was to assess RFS and OS in all patients with early stage EOC. Secondary objectives were to assess RFS and OS in early stage EOC with high-risk disease, predictors of RFS and OS, and outcomes of FSS. Survival probabilities were estimated according to Kaplan-Meier and compared by the log rank test. Cox's regression model was used to analyze the significance of various factors affecting relapse free survival (RFS) and overall survival (OS).195 patients with early stage EOC were recruited with median age of 47 years (range, 16-80 years). FIGO stage I and stage II were seen in 72 % and 18 % patients respectively. Serous subtype was reported in 58 % and high-grade histology in 66 %. 184 patients (94.0%) underwent optimal staging surgery, including 27 (14%) with fertility sparing surgery (FSS). 133 (91.7 %) of 145 patients with high-risk disease received adjuvant chemotherapy (paclitaxel and carboplatin), while 12 (8.3 %) patients opted to remain on observation. At median follow up of 56 months (95 % CI, 46-64 months), 49 (25 %) patients relapsed [including 3 of 27 (11.1 %) who underwent FSS], 18 patients died of progressive disease, while 31 patients were alive and disease free. Estimated OS at 5 years is 87.6 % (95 % CI 79.9-92.5) and RFS is 73.2 % (95 % CI 64.7-80.0). On multivariate analysis tumor grade was predictive of RFS (HR 2.9, p 0.04) and OS (HR 9.4, p 0.02).This study confirms the excellent outcome for patients with early stage EOC. Histological grade of tumor is a significant predictor of OS and RFS. FSS is feasible in selected patients with early EOC.

IntroductionCurrent risk predictors of multiple myeloma do not integrate ethnicity-specific information. However, the impact of ethnicity on disease biology cannot be overlooked. In this study, we have investigated the impact of ethnicity in multiple myeloma risk prediction. In addition, an efficient and robust artificial intelligence (AI)-enabled risk-stratification system is developed for newly diagnosed multiple myeloma (NDMM) patients that utilizes ethnicity-specific cutoffs of key prognostic parameters.MethodsK-adaptive partitioning is used to propose new cutoffs of parameters for two different datasets—the MMIn (MM Indian dataset) dataset and the MMRF (Multiple Myeloma Research Foundation) dataset belonging to two different ethnicities. The Consensus-based Risk-Stratification System (CRSS) is designed using the Gaussian mixture model (GMM) and agglomerative clustering. CRSS is validated via Cox hazard proportional methods, Kaplan–Meier analysis, and log-rank tests on progression-free survival (PFS) and overall survival (OS). SHAP (SHapley Additive exPlanations) is utilized to establish the biological relevance of the risk prediction by CRSS.ResultsThere is a significant variation in the key prognostic parameters of the two datasets belonging to two different ethnicities. CRSS demonstrates superior performance as compared with the R-ISS in terms of C-index and hazard ratios on both the MMIn and MMRF datasets. An online calculator has been built that can predict the risk stage of a multiple myeloma (MM) patient based on the values of parameters and ethnicity.ConclusionOur methodology discovers changes in the cutoffs with ethnicities from the established cutoffs of prognostic features. The best predictor model for both cohorts was obtained with the new ethnicity-specific cutoffs of clinical parameters. Our study also revealed the efficacy of AI in building a deployable risk prediction system for MM. In the future, it is suggested to use the CRSS risk calculator on a large dataset as the cohort size of the present study is 25% of the cohort used in the R-ISS reported in 2015.

Endometrial cancer (EC) is common malignancy in women and its incidence is slowly on the rise. Accurate surgical staging, with aggressive cytoreduction when indicated, remains the most critical step in the treatment. Careful pathological evaluation and/or molecular risk stratification guides for proper systemic adjuvant radiotherapy ± chemotherapy. Recurrent and metastatic EC has dismal prognosis and palliative therapies (chemotherapy, hormonal therapy or radiation) forms the backbone of treatment. There is an unmet need of newer therapies to improve survival in such cases. A number of tyrosine kinase inhibitors are currently under evaluation. Recent data on therapeutic targeting of HER2 positive serous EC is exciting. Data on check point inhibitors particularly based on biomarker select population has raised hope for potentially effective treatment for women with high risk endometrial cancer .

In cases of ovarian carcinoma, primary cytoreductive surgery (CRS) is the standard treatment up to stage IIIB, but patient selection for neoadjuvant chemotherapy (NACT) in selected cases is controversial. A total of 200 patients with advanced ovarian cancer were analyzed retrospectively, according to specific selection criteria. Primary CRS was performed in 95 patients (47.5%) and interval CRS after 3–6 cycles of NACT was performed in 105 patients (52.5%). After median follow-up of 35 months, 5-year overall survival was 53.7% in the upfront CRS group and 42.2% in the NACT group. Primary CRS is the standard in advanced stages of ovarian carcinoma, but in certain subset of patients, NACT is preferred. Identifying that group is challenging but feasible. Proper selection of patients is key to successful outcomes.

We used plerixafor in 'a risk adapted approach' for stem cell mobilization for multiple myeloma (MM) patients prior to autologous stem cell transplantation (ASCT).Between January, 2017 and December, 2019 105 consecutive patients of MM were recruited (Study Cohort). Patients received inj G-CSF 10 µg/kg in 2 divided doses for 5 days. Day 4 peripheral blood (PB) CD34+ count was used as a guide; if count was20 cells/µl, patients received plerixafor. For those with ≥ 20 cells/µl apheresis was commenced on day 5. We compared their outcome with 156 MM patients transplanted between 2012 and 2016 with G-CSF mobilized PB stem cells (Control Cohort). Primary end point was to collect ≥2.0 × 1096.2% of patients achieved ≥ 2.0 × 10Plerixafor in this risk adapted strategy resulted in successful mobilization, decreased time to engraftment and was cost effective.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). Methods A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. Results Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. Conclusions Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.