Dexamethasone-Free Antiemetic Prophylaxis for Highly Emetogenic Chemotherapy: A Double-Blind, Phase III Randomized Controlled Trial (CINV POD study).

PURPOSE: The effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) is not known. METHODS: This was a double-blind, phase III trial designed to show the noninferiority of a DEX-free regimen (olanzapine, palonosetron, and fosaprepitant [OPF]) compared with the DEX-containing regimen (olanzapine, palonosetron, and DEX [OPD]). Chemotherapy-naïve patients age 18-80 years receiving single-day HEC were randomly assigned 1:1 to receive either the OPD regimen or the OPF regimen. The primary objective was to compare complete response (CR) rates for vomiting during the overall period (start of chemotherapy to 120 hours). Secondary objectives included CR for vomiting during the acute period (0-24 hours) and delayed period (24-120 hours), CR for nausea, and comparison of toxicities and patient-reported outcomes. RESULTS: Three hundred forty-six patients received the study interventions, 174 in the OPD arm and 172 in the OPF arm. The DEX-free OPF arm had significantly higher CR rates for vomiting compared with the DEX-containing OPD arm in acute (94.7% v 85.6%; P < .004), delayed (81.9% v 50.5%; P < .001), and overall (79.6% v 48.8%; P < .001) periods. For nausea, CR rates in the OPF arm were higher in delayed (53.4% v 39.6%; P = .009) and overall (50.5% v 39.1%; P = .031) periods but not in the acute period (77.9% v 81.6%; P = .39). Fatigue (P = .009) and drowsiness (P = .002) were more in the OPF arm in the acute period and insomnia (P < .001) in the OPD arm in the overall period. CONCLUSION: This study shows that a DEX-free OPF regimen is efficacious and should be considered a standard option for acute and delayed CINV prophylaxis for HEC.

Forecasting factors and outcomes in hawkish inflammatory breast carcinoma - A single center data exploration.

INTRODUCTION: Inflammatory breast carcinoma (IBC) is an aggressive clinical syndrome of invasive breast carcinoma. There is paucity of data regarding the outcomes in IBC. OBJECTIVES: Analyses of OS and Event-free survival (EFS) in nonmetastatic and metastatic IBC and to find prognostic factors influencing them. METHODOLOGY: In this single center, retrospective study the data of patients fulfilling the clinical criteria of IBC were retrieved from 2016 to 2021. The impact of prognostic factors on OS and EFS were analysed by log rank test (univariate analysis). The OS and EFS were depicted as Kaplan Meier survival curves. RESULTS: There were 22 patients with IBC. Median follow-up was 17 months. The median OS was significantly better in non-metastatic(M0) compared to metastatic IBC (25 months vs 6 months) with 3year OS rate of 50% vs 0% respectively. The post-menopausal status, grade 2 histology and trimodality treatment showed better outcome while N3 stage at diagnosis had worse outcome in M0 group. The lesser HR expression, lesser pCR rates, higher N3 proportion, liver metastasis and multiple metastatic site involvement contributed to the worse outcome observed in this study. CONCLUSION: The aggressive clinicopathological features of IBC in the present study resulted in less favourable outcome compared to literature review. Improved outcome with trimodality highlights the emergent need for additional targeted therapy to improve pCR and operability.

Therapeutic Outcomes in High-Grade B-Cell Lymphoma, NOS: Retrospective Analysis.

The nomenclature high-grade non-Hodgkin's lymphoma was repurposed in the World Health Organization (WHO) 2016 update as high-grade B cell lymphoma (HGBL). However, among the HGBL entities HGBL, not otherwise specified (NOS) remains a poorly described entity with a lack of literature regarding its treatment and prognosis. The baseline characteristics, treatment, and outcome of HGBL, NOS cases were analyzed. Thirty HGBL, NOS patients were diagnosed between January 2017 and December 2019. Their median age was 49.3 years, and 30% had advanced IPI. The majority received R-CHOP chemotherapy, while five patients received dose-adjusted R-EPOCH. At a median follow-up of 15 months, nine patients had disease progression or relapse. EFS and OS were 22 months (12.1-31.9 months) and 37 months (29.4-44.0 months) respectively. Only NCCN-IPI ≤ 2 showed significant influence on the outcome. The results were similar to the outcomes previously reported. This study highlights the importance of NCCN-IPI in ascertaining the prognosis of HGBL, NOS. The literature review suggests that more intensive chemotherapy is ideal for HGBL, NOS. However, prospective trials are needed to prove whether the treatment of HGBL, NOS can be tailored based on NCCN-IPI.

The continuing conundrum in oligometastatic breast carcinoma: A real-world data.

The optimal management in Oligometastatic (OM) breast carcinoma is not defined. OBJECTIVES: To identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM. METHODOLOGY: Patients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS. RESULTS: There were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67. CONCLUSION: The survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.

Autologous Stem Cell Transplantation in Testicular Germ Cell Tumor-Preliminary Experience from a Single Center.

Background Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be salvaged with systemic therapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Complete remission can be obtained in approximately 50 to 60% of patients treated with HDCT. Our experience reports the efficacy and safety of HDCT followed by ASCT in relapsed GCT. Methods Analysis of patient records (2012-2019) showed that three patients had received HDCT and ASCT. Results All the three patients were treated with BEP (bleomycin, etoposide, and cisplatin) as first-line therapy. HDCT was done in Case 1 after third-line salvage and in other two patients after second-line salvage chemotherapies. High-dose carboplatin and etoposide were used as conditioning regimen. Granulocyte colony-stimulating factor was used for the mobilization of stem cells. After ASCT, complete remission was documented in all the patients. All were alive and disease-free till the last follow-up. Grade ¾ toxicities including myelosuppression, diarrhea, and mucositis were observed in all three patients. Conclusion This is the first report from India on HDCT with ASCT in GCT. HDCT/ASCT seems to be feasible, safe, and effective in relapsed testicular GCTs.

Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia's: Experience from a Cancer Center in India.

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014-2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan-Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.

COVID19 in children with cancer in low- and middle-income countries: Experience from a cancer center in Chennai, India.

Crowded outpatient clinics and common wards in many hospitals in low and middle-income countries predispose children, caregivers, and health care workers to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on the clinical features and outcomes of 15 children with cancer at our center who tested positive for SARS-CoV-2. Five out of 15 patients were symptomatic, and one patient required intensive care and respiratory support. All the patients in the study have recovered from the SARS-CoV-2 infection without any sequelae and have resumed their cancer treatment.

Plasmablastic lymphoma - single centre experience with infusional EPOCH chemotherapy.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare type of aggressive large B - cell non-Hodgkin Lymphoma (NHL) which was initially described in HIV positive individuals and later was also described in immune-competent individuals. It was included as a distinct entity in the WHO lymphoma classification in 2008. METHODS: The clinical features, HIV status, treatment details, and outcomes of patients diagnosed with plasmablastic lymphoma from January 2012 to December 2018 were retrospectively collected from the patient records and analyzed. The survival analysis was done by Kaplan Meier analysis and the comparison was done by the Log Rank test. RESULTS: The median age of 25 patients, included in the study was 41 years (Range 13-71 years). Males constituted 76 %. HIV positivity was 72 %. Stage IV disease was present in 76 %. Extranodal involvement was seen in 96 %. Out of 25 patients, seven did not receive any treatment and three received metronomic oral chemotherapy due to poor performance status at presentation. Fifteen patients received chemotherapy on a curative intent. Infusional EPOCH chemotherapy was given in 13 patients. CHOP and CHOEP chemotherapy was given in one patient each. The median number of cycles was 6 (Range: 3-8). The overall response rate of patients treated on a curative intent was 80 % (Complete response and partial response in 8 and 4 respectively). Three patients underwent high dose chemotherapy with autologous stem cell rescue at first remission. The median event-free survival (EFS) and median overall survival (OS) of the whole study population was 5.9 and 12.4 months respectively, with a median follow of 26.9 months. The median EFS was 13.8 months and the median OS was not reached in the curative-intent group. The factors adversely influencing the EFS and OS were Age > 40 years, high IPI, and non-curative intent of treatment. CONCLUSION: Plasmablastic lymphoma commonly presents as stage 4 disease with extranodal involvement and is more common in immune-deficient individuals. Infusional EPOCH chemotherapy is a promising option that induces long term remission.

The Effect of High Dose Rate Interstitial Implant on Early and Locally Advanced Oral Cavity Cancers: Update and Long-Term Follow-Up Study.

Introduction Brachytherapy, with or without external beam radiation therapy (EBRT), can be an alternative to surgery for organ preservation in early and locally advanced oral cavity cancers. This study aims to evaluate the effect of high dose rate (HDR) interstitial brachytherapy on early and locally advanced squamous cell carcinoma (SCC) of the oral cavity when used alone or as a boost to EBRT. Methods A total of 125 patients with histologically proven stage T1-3/N0-1 SCC of the oral cavity were included in the study. A total of 15 patients with stage I disease received an interstitial implant dose of 3,850 cGy at 350 cGy per fraction, two fractions a day. Another 53 patients had stage II, and 57 patients had stage III disease; these patients received EBRT of 50 Gy in 25 fractions along with an HDR brachytherapy boost of 21 Gy in seven fractions of 3 Gy per fraction twice daily. The stage III patients also received concurrent chemotherapy with injections of cisplatin (70 mg/m2) given every three weeks for three days in divided doses. All node-positive patients received a boost to the node of up to 64 Gy by external beam radiation. Disease response rates, five-year disease-free survival rates, and toxicities were analyzed. Results The median follow-up was 60 months. Among the patients, 103 (82.4%) had a complete response, while 22 (17.6%) had residual disease and were referred for surgical salvage. The five-year disease-free survival was 100% in stage I, 83% in stage II, and 77.2% in stage III; 4% of patients developed grade 3 acute skin toxicity and 23.2% developed acute grade 3 mucositis. Eleven patients died during the follow-up period. Two patients died due to myocardial infarction but had achieved a complete tumor response. One patient had pulmonary tuberculosis and died due to fulminant infection after three years of disease-free survival period. One patient developed a second primary in the brain stem that presented with quadriplegia and expired. Seven patients died due to the progression of the initial disease. Conclusions Proper brachytherapy technique and meticulous planning can minimize the toxicity while providing better tumor control and achieve high local control rates. Brachytherapy, with or without EBRT, can be a surrogate to surgery in early oral cavity cancers as it can achieve organ preservation while providing good functional outcomes.

Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced vomiting in children: An open-label, randomized phase 3 trial.

BACKGROUND: Breakthrough chemotherapy-induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open-label, single-center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV. PROCEDURE: Children aged 5-18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms. RESULTS: Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm. CONCLUSION: Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.

Role of high dose rate interstitial brachytherapy in early and locally advanced squamous cell carcinoma of buccal mucosa.

BACKGROUND: The study aimed to assess the effect of High Dose Rate (HDR) Interstitial Brachytherapy when used alone or in combination with External Beam Radiotherapy (EBRT), in early and locally advanced squamous cell carcinoma of buccal mucosa. MATERIALS AND METHODS: Thirty three patients with histologically proven squamous cell carcinoma of the buccal mucosa received high dose rate interstitial brachytherapy either as primary treatment or as a boost from November 2008 to April 2013. Stage I patients received interstitial brachytherapy alone to a dose of 38.50 Gy, 3.5 Gy per fraction, twice daily at six hours apart for 11 fractions. Stage II patients received EBRT to a dose of 50 Gy in 25 fractions of two Gy each followed by brachytherapy boost to 21 Gy, 3.5 Gy per fraction, twice daily at six hours apart for six fractions. Stage III patients received the same radiotherapy schedule (i.e., same EBRT & Brachytherapy schedule) and with addition of Injection Cisplatin 70 mg/m(2) in three divided doses every three weeks along with EBRT. RESULTS: Follow up ranged from 12 to 60 months, median follow up was 26 months. Complete response was observed in 28 patients. Five patients had residual disease and were referred for surgical salvage. One patient died of disease progression. Stage I patients had 100% local control, whereas Stage II and Stage III patients had 84.6% and 80% local control respectively. CONCLUSION: HDR Interstitial Brachytherapy used either as a primary treatment modality or as a boost in buccal mucosal cancers provides results comparable to that of surgery, with the advantages of organ preservation, better cosmetic and functional outcomes.