Cardiac Autonomic and Endothelial Function in Acute Lymphoblastic Leukaemia Patients Immediately After Chemotherapy and at the Three-Month Follow-up.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malignant uncontrolled overproduction of immature lymphoid cells in blood and bone marrow. The primary treatment of ALL is chemotherapy. Chemotherapy can have myriad systemic side effects, notably cardiovascular derangement. Autonomic derangement occurrence in cancer patients signifies cardiovascular risk in them and is a determinant of cardiovascular morbidity and mortality. Elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels implicated in the regulation of inflammation indicate endothelial dysfunction. High levels of high-sensitivity C-reactive protein (hsCRP) can be indicative of low-grade inflammation. Hence, in this study the cardiac autonomic function and endothelial and inflammatory biomarker levels in adult patients with ALL were assessed immediately and three months after chemotherapy. METHODS: In this longitudinal study, 30 ALL patients (23 males, seven females) aged between 18 to 50 years, who had completed chemotherapy regimens, and 30 age and gender-matched healthy participants (controls) were recruited. Cardiac autonomic function tests (short-term heart rate variability (HRV), 30:15 ratio, synaptic excitation and inhibition (E/I) ratio, diastolic blood pressure (DBP) response to isometric hand grip), endothelial markers (sVCAM-1 and sICAM-1), and inflammatory marker (hsCRP) were assessed immediately and at three months after chemotherapy. RESULTS: Magnitudes of time domain and frequency domain indices, conventional autonomic function test indices, and biomarkers were deranged in ALL patients immediately after chemotherapy. After three months, cardiac autonomic function parameters were found to improve in the form of increased root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of the interbeat intervals of normal sinus beats (SDNN), total power, high-frequency (HF)nu, and decreased low-frequency(LF)nu & LF-HF ratio. Endothelial (sVCAM-1) and inflammatory markers (hsCRP) were lower in the patient group as compared to the controls immediately after chemotherapy. Three months after chemotherapy, the levels of endothelial and inflammatory markers did not show much change. CONCLUSION: In this study, we found ALL patients showed higher sympathetic drive, decreased parasympathetic modulation, and sympathovagal imbalance immediately after chemotherapy as compared to the controls, indicating cardiovascular risk. After three months, improvement in cardiovascular autonomic function was observed. ALL itself is a state of inflammation with elevated endothelial and inflammatory markers; thus, the decreased endothelial and inflammatory markers could be attributed to the immediate effect of chemotherapy.

Impact of Genetic Polymorphisms in NF-ĸB2 and TRAF3 Genes on Response to Bortezomib-Based Therapy in Multiple Myeloma Patients.

BACKGROUND: Multiple myeloma (MM), being the second most common hematological malignancy, has garnered significant attention. The ubiquitin proteasomal pathway (UPP), crucial for normal cell function, plays a pivotal role in myeloma pathophysiology, especially with the advent of bortezomib (BTZ). Dysregulation of the UPP has implications ranging from developmental abnormalities to cancer. OBJECTIVES: This study aimed to delineate the clinical characteristics of newly diagnosed multiple myeloma patients and investigate the influence of single nucleotide polymorphisms (SNPs) in NF-ĸB2 and TRAF3 genes on the risk and treatment response to bortezomib-based chemotherapy. MATERIALS AND METHODS: Conducted at JIPMER, Pondicherry, this prospective study enrolled 184 participants, comprising cases and controls. DNA extraction from peripheral blood samples was followed by SNP analysis through Real-time Polymerase Chain Reaction. Patients were categorized into Good and Poor responders, and SNP associations with treatment response, response rates, and survival outcomes were assessed using chi-square and Kaplan-Meier analyses. RESULTS: The median age of participants was 55 years, with backache being the most prevalent symptom (66.3%). Hypercalcemia (22%), renal failure (8.7%), and bone fractures (45.7%) were also observed, alongside high prevalence of anemia. Notably, the frequency of the TRAF3 rs12147254 A allele was lower in cases compared to controls (31% vs. 49%, P-value=0.002). Poor responders exhibited higher frequencies of the GA+AA genotypes in TRAF3 rs12147254 (OR-3.882(1.629-9.251), P-value-0.002) and NFKB2 rs1056890 (OR-3.308(1.366-8.012), P-value-0.008) when compared to good responders. The GA+AA genotype in TRAF3 rs11160707 SNP correlated with improved progression-free survival. CONCLUSION: The study findings underscore a significant association between genetic polymorphisms and treatment response outcomes, suggesting their utility in prognostic determinations and clinical outcomes prediction in multiple myeloma patients.

Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

PURPOSE: Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. OBJECTIVES: The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. METHODS: In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. RESULTS: In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. CONCLUSION: In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Aggressive Histology and Extensive Metastasis Characteristic of Very Young Gastric Cancer (Less Than 30 Years): A Retrospective Clinical Audit.

Narendran KrishnamoorthiObjectives Gastric cancer (GC) is an aggressive disease and remains one of the most common causes of cancer-related mortality worldwide. Incidence of gastric cancer in young (GCY) varies between 2 and 8%. GCY faces unique challenges such as biological variation, diagnosis at an advanced stage, issues related to fertility preservation, and psychosocial considerations. This study aimed to find the differences in clinical characteristics and treatment outcomes of GCY compared to gastric cancer in older adults (GCO). Material and Methods This is a retrospective study from a tertiary care center. We screened records from 2015 to 2020, identified 33 records of GCY (less than 30 years), and compared the data with GCO (greater than 30 years) during 2015 and 2018. Results We identified 33 patients with GCY with a median age of 28 years (21-30) and a female to male ratio of 2:1. In GCY, 60% of patients presented with metastatic disease. Diffuse-type histology was more common in the GCY than in GCO (66.7% vs. 41.7%, p = 0.001). In patients with metastasis, multiple metastases were common in GCY compared to GCO (45% vs. 15%, p = 0.003). The median duration of follow-up for all patients was 27 (24-29) months. In GCY, the median OS was not reached for patients treated with curative intent, and it was 13 months for those treated with palliative intent. Conclusion The incidence of GCY in our study was like the western literature. Female patients with aggressive diffuse histology and multiple extensive metastases were characteristic of GCY. The survival outcomes were identical to GCO.

Clinicopathological features and survival outcomes for gastric adenocarcinoma: Real-world single-center data.

INTRODUCTION: Gastric cancer is the fifth most-common cancer and fourth common cause for cancer-related deaths globally. Surgery preceded or followed by chemotherapy or chemoradiotherapy is considered an optimal treatment for locally advanced gastric cancer. This study is a real-world data from a tertiary referral institute in southern India, in its experience with treating gastric adenocarcinoma over a period of four years with a minimum of two-year follow-up. METHODS: This was a retrospective analysis of data of patients with histologically proven gastric adenocarcinoma enrolled in the Department of Medical Oncology from 2015 to 2018. The demographic details, presentation, staging, treatment received and outcomes of patients with gastric adenocarcinoma were collected and analyzed in this study. RESULTS: Total 488 patients with gastric adenocarcinoma were included for the study. The stage-wise distribution of patients revealed early and locally advanced (45%) and metastatic (55%). The peritoneum and liver were the common sites of metastasis. The treatment distribution of these patients included perioperative chemotherapy followed by surgery (25 [5%]), surgery followed by adjuvant chemotherapy (65 [13%]), surgery alone (16 [3%]), perioperative chemotherapy alone (23 [4%]), palliative chemotherapy (274 [56%]) and supportive care (85 [17%]). The median overall survival for curative, palliative and supportive treatment was 23 (18-28), nine (7.6-10.4) and four (2.7-5.3) months, respectively. The two-year overall survival in the intention to treat population in the primary surgery (n = 81) and perioperative chemotherapy groups (n = 66) was 67.4% vs. 29.9% (p < 0.0001), respectively. CONCLUSION: This study highlights the advanced nature of the presentation of gastric cancer patients and the poor rate of treatment completion. The median survival rates in curative patients remain to be dismally poor. The treatment sequence in curable gastric cancer of surgery followed by adjuvant chemotherapy vs. perioperative chemotherapy followed by surgery needs to be explored in our country.

Extragonadal Germ Cell Tumors: A Single Institution Experience with Clinicopathological Correlation.

Background. Extragonadal germ cell tumors (EGCTs) are a rare heterogeneous group of tumors without evidence of primary gonadal germ cell tumors. They account for 2%-5% of overall malignancies. EGCTs are often not clinically suspected, making them challenging for pathologists. In this retrospective observational study, we describe our institutional experience among EGCTs with clinicopathological correlation. Materials and methods. All patients diagnosed as EGCTs from January 2014 to April 2023 were collected. All relevant clinical data and serum markers were retrieved from hospital medical records. Histopathology and immunohistochemistry slides were reviewed. Results. The present study included a total of 56 patients; 34 (60%) men and 22 (40%) women with a men-to-women ratio of 1.5:1. Of them, 1 patient had congenital/neonatal EGCTs, 21 patients had prepubertal EGCTs, and 34 had post-pubertal EGCTs. The common sites included are mediastinum (45%), sacrococcyx (18%), retroperitoneum (14%), and central nervous system (12%). The other rare sites were the vagina, liver, colon, and duodenum. The common germ cell tumor included mature teratoma (34%), mixed germ cell tumor (27%), seminoma/germinoma (12%), pure yolk sac tumor (11%), immature teratoma (9%), mature teratoma with somatic tumor (5%), and embryonal carcinoma (2%). All histological diagnoses of germ cell tumors were confirmed with IHC markers like PLAP, CD117 (KIT), AFP, LIN28, CD30, and ß-hCG. Pre and posttreatment serum tumor marker levels were available in 37 patients. All our treated patients had a decrease or normal tumor marker levels post-therapy. Conclusion. In our study, a heterogeneous group of germ cell tumors was seen. Most of them were seen in post-pubertal adolescents and young adults. Early intervention by platinum-based combination chemotherapy in seminoma and nonseminomatous germ cell tumors has significantly improved the prognosis of malignant EGCTs similar to their germ cell counterparts.

Quantification of circulating clonal plasma cells by multiparametric flow cytometry as a prognostic marker in patients with newly diagnosed multiple myeloma.

BACKGROUND: Studies have shown that the quantification of circulating clonal plasma cells (cCPCs) in peripheral blood using flow cytometry could be used as a prognostic predictor of poor outcome in multiple myeloma (MM). METHODS: In 66 newly diagnosed MM, cCPCs were quantified (cCPC%) and analysed for association with outcome and survival. Single-tube combined surface (CD45/CD19/CD138/CD38/CD56/CD27/CD81 as per availability) and cytoplasmic (kappa/lambda) staining was done using pre-titrated volumes of antibodies. In 26 patients, repeat cCPC% was assessed post-induction therapy. For association studies, treatment response has been taken as good (VGPR and above) and poor (PR and below). All statistical analyses were performed with SPSS software version 16.0. RESULTS: There was no significant association between cCPC% at baseline with staging (p = 0.43), ß2 -microglobulin (p = 0.27) and albumin (p = 0.08). There was a significant difference between the pre-induction and post-induction cCPC% (p = 0.0001). The patients were segregated using a cut-off of ≥0.197 and <0.197 based on the median values of baseline cCPC%. The post-induction outcome was available for 47 patients among whom 33 (70%) had VGPR and above. There was a significant association between higher cCPC% at baseline with poor treatment response (p = 0.008). The median OS in the study patients was 42 (CI 28.14-43.03) months and the median PFS was 39 (CI 28.49-49.04) months. Higher cCPC% showed a lower median PFS (30 vs. 39 months) and OS (35 vs. 41 months) compared to lower cCPC% though it was not statistically significant. CONCLUSION: Flow cytometric baseline cCPC% in newly diagnosed MM was associated with poor treatment response and survival.

Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy.

INTRODUCTION: The burden and mechanisms of endocrine therapy-related bone loss are well known, while there are limited data on chemotherapy-induced bone resorption. The study aimed to evaluate the effect of cytotoxic chemotherapy on bone homeostasis among postmenopausal women with non-metastatic breast cancer. MATERIALS AND METHODS: Early and locally advanced postmenopausal non-metastatic breast cancer patients aged 45 to 65 planned for three cycles of anthracycline and four cycles of taxane chemotherapy administered along with dexamethasone (cumulative dose-256 mg) as an antiemetic from June 2018 to December 2021 were included. Bone mineral density (BMD), bone turnover markers, calciotropic hormones, pro-inflammatory cytokines, oxidative stress, and total antioxidant levels (TAS) were measured. RESULTS: We recruited 109 patients, with early 34 (31.2%) and locally advanced breast cancer 75 (68.8%) with median age 53 (45-65) years. There was a significant decrease in the % BMD at the lumbar spine, neck of the femur, and total hip post-chemotherapy. There was a significant increase in serum C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels post-chemotherapy. PINP/CTX ratio significantly decreased post-chemotherapy. Serum 25-OH vitamin D was significantly reduced with a compensatory increase in plasma iPTH levels. The change in CTX, PINP/CTX ratio, 25-OH vitamin D, iPTH, and oxidative stress index was more pronounced during anthracycline as taxane chemotherapy. There were no significant changes in pro-inflammatory cytokine levels. CONCLUSION: Chemotherapy and dexamethasone as antiemetic resulted in significant bone loss, as evidenced by bone turnover markers. Further studies are required to understand the mechanism of chemotherapy-induced bone loss and the need for bone-strengthening agents during chemotherapy.

Practice Patterns and Survival in Patients with Resected Pancreatic Ductal Adenocarcinomas (PDAC) - Results from the Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) Study.

BACKGROUND: There is limited data from India with regard to presentation, practice patterns and survivals in resected pancreatic ductal adenocarcinomas (PDACs). METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) included data from 8 major academic institutions across India and presents the outcomes in upfront resected PDACs from January 2015 to June 2019. RESULTS: Of 288 patients, R0 resection was achieved in 81% and adjuvant therapy was administered in 75% of patients. With a median follow-up of 42 months (95% CI: 39-45), median DFS for the entire cohort was 39 months (95% CI: 25.4-52.5), and median overall survival (OS) was 45 months (95% CI: 32.3-57.7). A separate analysis was done in which patients were divided into 3 groups: (a) those with stage I and absent PNI (SI&PNI-), (b) those with either stage II/III OR presence of PNI (SII/III/PNI+), and (c) those with stage II/III AND presence of PNI (SII/III&PNI+). The DFS was significantly lesser in patients with SII/III&PNI+ (median 25, 95% CI: 14.1-35.9 months), compared to SII/III/PNI + (median 40, 95% CI: 24-55 months) and SI&PNI- (median, not reached) (p = 0.036)). CONCLUSIONS: The MIPPAP study shows that resectable PDACs in India have survivals at par with previously published data. Adjuvant therapy was administered in 75% patients. Adjuvant radiotherapy does not seem to add to survival after R0 resection.

Does the Inclusion of CD34+ B-cell Progenitors (Hematogones) in Stem Cell Enumeration of Apheresis Product Using ISHAGE Protocol Affect the Final Harvest dose Adequacy and the Outcome of Transplantation? A Single Institution Experience from Southern India.

Purpose: Hematogones have similar antigenic and light scatter properties when compared to CD34+ hematopoietic stem cells (HSC) but they form a separate cluster with dimmer CD45 expression. These should be excluded while enumerating HSC, as their inclusion can overestimate and hence affect the final dose of HSC. However, their exact impact on the outcome of HSC transplant (HSCT) is not entirely known and hence this study was undertaken to address these issues, if any. Methods: This was a retrospective study in which patients undergoing HSCT were included, and flow cytometric enumeration was done on the apheresis product using single platform ISHAGE protocol. The gating of all plots was reviewed and carefully studied for hematogone population which would have otherwise been included in the original gating. Results: Totally 78 patients underwent HSCT during the study period. On re-analysis, it was found that 10/78 (12.8%) cases had a separate hematogone population which was included in the HSC in the original analysis. Out of these 10 cases, 7/51 and 3/27 were in autologous and allogenic subgroup respectively. However, all the ten cases ultimately had adequate final stem cell dose and had successful engraftment. Conclusion: The inclusion of hematogones in CD34+ HSC enumeration of apheresis products did not yield any impact on neither the final dose nor the outcome of transplant in this study. However, it is recommended to exclude them from the final count when they are > 10% of the final HSC lest it overestimate the final harvest dose and outcome of HSCT.

Primary Pediatric Yolk Sac Tumor of Liver With Lung Metastasis: An Unusual Presentation With Diagnosis Aided by LIN28 Immunohistochemistry.

Yolk sac tumor is a malignant germ cell tumor, which typically occurs in the gonads with elevated serum alpha-fetoprotein (AFP). Among extragonadal sites, the liver is an uncommon location for primary pediatric yolk sac tumors. Other common hepatic tumors in this age group presenting with elevated serum AFP like hepatoblastoma and hepatocellular carcinoma must be differentiated from yolk sac tumors for initiating appropriate treatment and accurate prognostication. Lung metastasis with refractoriness to chemotherapy is an extraordinary presentation that has never been documented in the literature. We report our experience with a 2-year-old female child initially misdiagnosed as hepatoblastoma. It was found that LIN28 positivity by immunohistochemistry aided in confirmation of the histopathological diagnosis of primary yolk sac tumor of the liver.

Optimising platelet usage during the induction therapy of acute myeloid leukaemia: Impact of physician education.

INTRODUCTION: Platelet products are scarce and expensive resources to be used judiciously. However, inappropriate usage is common. Lack of physician awareness is an important issue. We implemented a physician education program (PEP) along with repeated WhatsApp reminders at our centre. We audited the platelet usage practise before and after the intervention. METHODS: Charts of patients with acute myeloid leukaemia (AML) treated between January 2020 and August 2020 was reviewed, and the mean platelet usage per patient per day was calculated. Physician education was implemented between September 2020 and December 2020 (2 PowerPoint lectures of 20 min each and weekly WhatsApp messages containing the guidelines). Data of patients treated between Jan 2021 and August 2021 was prospectively audited to understand platelet usage and the indications for transfusions. The British Committee for the Standards in Haematology (BCSH) platelet transfusion guidelines were used as the adjudication tool to evaluate compliance. The mean platelet usage per day per kg body weight of a patient before and after the PEP was compared using the t-test. RESULTS: Group A (before physician education) consisted of 22 patients, and group B (after physician education) consisted of 23 patients. The mean number of platelet transfusions for each patient in a day per kg body weight was 125.7 × 108 in group A whereas, after the PEP, it had reduced to 73.9 × 108 amounting to an absolute reduction of 51 × 108 (58.8%) from the baseline with a statistical significance of P = 0.001. After implementing the PEP, the mean number of random donor platelets used reduced by 10.25 units (34% reduction), and the mean single donor platelets used reduced by 0.83 units (19% reduction). The 190 requests for platelet transfusion received during this period were classified as appropriate (157/190), which constituted 82.63% of the requests, or inappropriate (33/190), which accounted for 17.36%. CONCLUSIONS: A short-duration education programme supplemented with weekly WhatsApp messages and an active feedback mechanism on the rationale of platelet transfusion by the treating physician and transfusion specialist could significantly reduce platelet consumption during the therapy of acute myeloid leukaemia patients. This is a measure that can be considered by all high-volume haematology centres, which can improve patient safety and reduce costs.

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer.

PURPOSE: Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy. METHODS: Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity. RESULTS: We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P < .001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal. CONCLUSION: Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study.

Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. We used Fleming's two-stage design for sample size calculation. We included transplant-eligible and ineligible patients aged 18-75 years in the study. The patients received four cycles of VPd induction followed by response assessment. Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32-72). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Three patients had high-risk cytogenetic abnormalities. After four cycles of VPd induction, ten patients (32%) achieved stringent CR, nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had PR. Fifteen (48%) had a complete metabolic response (CMR) on PET-CT. Two patients developed SAEs. Anemia was the most common hematological toxicity. Peripheral neuropathy and constipation were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Our study showed VPd induction is safe and efficacious in NDMM. Further Phase 3 studies are necessary to establish the superiority and survival benefits.

Cytotoxic chemotherapy is associated with decreased bone mineral density in postmenopausal women with early and locally advanced breast cancer.

PURPOSE: The burden and mechanisms of endocrine therapy-related bone loss have been studied in detail. However, there is limited data regarding cytotoxic chemotherapy's impact on bone health. There are no definitive guidelines for bone mineral density (BMD) monitoring and treatment with bone-modifying agents during cytotoxic chemotherapy. The study's primary objective was to evaluate the changes in BMD and fracture risk assessment tool (FRAX) scores among breast cancer women on cytotoxic chemotherapy. METHODS: One hundred and nine newly diagnosed early and locally advanced postmenopausal breast cancer patients planned for anthracycline and taxane-based chemotherapy were recruited prospectively during the study period from July 2018 to December 2021. BMD of the lumbar spine, the femoral neck, and the total hip were assessed by dual-energy X-ray absorptiometry scan. BMD and FRAX scores were evaluated at baseline, end of chemotherapy, and 6 months of follow-up. RESULTS: The median age of the study population was 53 (45-65) years. Early and locally advanced breast cancers were seen in 34 (31.2%) and 75 (68.8%) patients, respectively. The duration of follow-up between two BMD measurements was 6 months. The percentage of decrease in BMD at the lumbar spine, femoral neck, and total hip were - 2.36 ± 2.90, - 2.63 ± 3.79, and - 2.08 ± 2.80, respectively (P-value = 0.0001). The median risk of major osteoporotic fracture (MOF) at 10 years (FRAX score) increased from 1.7 (1.4) to 2.7% (2.4) (P-value = 0.0001). CONCLUSION: This prospective study in postmenopausal breast cancer women shows a significant association of cytotoxic chemotherapy with the worsening of bone health in terms of BMD and FRAX score.

Comparison of Efficacy of Aspirin Plus EOX vs. EOX Alone in Patients with Locally Advanced and Metastatic Gastric Cancer: a Randomized Clinical Trial.

PURPOSE: The role of aspirin in cancer prevention has been well defined; the last decade revealed its therapeutic role with improved efficacy when aspirin was added to capecitabine in heavily pre-treated metastatic colorectal cancer. Aspirin affects tumour growth through the PI3K pathway, which regulates apoptosis and autophagy. The objective was to compare the efficacy of aspirin plus epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy versus EOX alone in locally advanced and metastatic gastric cancer. METHODS: All patients with advanced gastric cancer reporting to the Department of Medical oncology between March 2017 and May 2019 were screened for study eligibility. They were randomly assigned to standard EOX with or without aspirin at a daily dose of 150 mg. Tumour measurements were assessed at baseline and after 3-4 cycles by an independent blinded radiologist according to RECIST criteria 1.1. Toxicity profiles were recorded as per CTCAE v 4.03. Per-protocol group was identified as 70 patients. The primary endpoint was overall response rates in the per-protocol group (defined as patients who received a minimum of 3 cycles and had an evaluable response after randomization). The secondary endpoints included toxicity analysis, progression-free survival, and overall survival. RESULTS: Ninety-five patients who fulfilled the study inclusion and exclusion criteria were randomized to group 1 EOX (50) or group 2 EOX plus aspirin (45). Seventy patients were included for the per-protocol analysis. The overall response rate in group 1 was 27% compared to group 2, which was 42%, P = 0.176. The median duration of follow was 29 (18.56-39.45) months. The median overall survival (n = 95) of group 1 versus group 2 was 11 (8.58-13.42) months and 10 (6.86-13.14) months, respectively, P = 0.90. There was no statistical significance in the overall survival per-protocol analysis (n = 70) between group one 12 (8.75-15.25) months versus group two 12 (6.21-17.79) months, P = 0.50. CONCLUSIONS: There was no improvement in the response rates, progression-free survival, and overall survival on adding aspirin to EOX chemotherapy in locally advanced and metastatic gastric cancer in an unselected population. A further role of PI3K mutation as a biomarker needs to be evaluated in this setting.

Pattern of expression of CDX2 in colorectal cancer and its role in prognosis.

Background: CDX2, a nuclear protein, is essential for the proliferation and development of intestinal epithelial cells and is frequently down-regulated during tumorigenesis. We have evaluated the pattern of CDX2 expression in all stages of colorectal cancer (CRC) and its association with prognosis. Methods: We performed CDX2 staining by immunohistochemistry (IHC) on the available biopsy blocks of patients of CRC registered in our institute from January 2014 to January 2018. CDX2 scoring was done using the semi-quantitative method. Results: A total of 286 patients were registered during the study period, of which only 110 biopsy blocks were available for staining. Of 110 patients, 77 (70%) had colon cancer and 33 (30%) had rectal cancer. The median age was 54.2 years, with 62 (56.4%) being male and 48 (43.6%) female with a male to female ratio of 1.3:1. In the study cohort, 33 (30%) patients had stage II disease, 30 (27.3%) had stage III, and 47 (42.7%) had stage IV. Seventy-three (66.4%) were positive for CDX2 and 37 (33.4%) were negative. Loss of CDX2 expression was significantly associated with advanced stage, rectal site, poor grade of differentiation, and presence of lymphovascular invasion. With a median follow-up of 16 months, progression-free survival (PFS) at 2 years was 30% for CDX2-negative patients compared to 67% for CDX2-positive patients (P = 0.009), whereas the overall survival (OS) at 2 years was 46% for CDX2-negative versus 77% for CDX2-positive patients (P = 0.01). Conclusion: Loss of CDX2 expression is associated with advanced stage, higher tumor grade, presence of LVSI, worse PFS, and OS and thereby functions as a poor prognostic factor in CRC.

Plerixafor use in autologous hematopoietic stem cell mobilization: Experience from a single center in Southern India.

BACKGROUND: Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute. METHODS: This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level. RESULTS: During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use. CONCLUSION: A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome.

An Audit of Delays in the Management of Non-Metastatic Osteosarcoma at a Tertiary Care Center in South India.

Background and objective Delays in the management of osteosarcoma (OGS) lead to tumor progression and the development of metastasis, resulting in a decrease in overall survival (OS). The primary objective of this study was to determine whether delays occur in implementing the individual steps in the management of OGS in South India. Methods In this study, core biopsy reports between October 2019 and October 2021 were retrospectively examined for a diagnosis of OGS. The primary outcome variables in this study were time to MRI, time to biopsy, time to biopsy report, time to neoadjuvant chemotherapy (NACT), time to surgery, and time to adjuvant chemotherapy (ACT). Statistical analysis was performed by comparing the outcome variables with the hypothesized mean. Results There were 38 patients with primary non-metastatic OGS. Of these, 92% received NACT, and 74% completed full treatment. The mean time to MRI was 11.3 ± 6.7 days, mean time to NACT was 15.3 ± 12.7 days, mean time to surgery was 31.1 ± 15.3 days, and mean time to ACT was 29.7 ± 10.1 days. Time to MRI was more than seven days in 68% of the cases, while time to NACT was more than seven days in 74%. Time to surgery was more than 21 days in 83% of the cases, and time to ACT was more than 21 days in 82% of the cases. Conclusion Based on our findings, there is a significant delay (p<0.05) in time to MRI, time to NACT, time to surgery, and time to ACT. The delay in time to surgery is more than the delay in time to MRI, time to NACT, and time to ACT. The delay is due to a variety of reasons, the most common being the long waiting period at the hospital.