Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis.

In this editorial we comment on the article by Wei et al, published in the recent issue of the World Journal of Clinical Oncology. The authors investigated the role of Transmembrane 9 superfamily member 1 (TM9SF1) protein in bladder cancer (BC) carcinogenesis. Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines. These cell lines were then subject to cell counting kit 8, wound-healing assay, transwell assay, and flow cytometry. Proliferation, migration, and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression. TM9SF1 silencing inhibited proliferation, migration and invasion of BC cells. The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Hypofractionation for Regional Nodal Irradiation in Breast Cancer: Best of Both the Worlds.

Locoregional radiotherapy play an important role in controlling the disease after surgery in patients with breast cancer. Radiotherapy schedules vary from conventional fraction to hypofractionation. The purpose of this review is to get an insight into the data on regional nodal irradiation (RNI) with hypofractionation in patients with breast cancer. This systematic review was constructed in accordance with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework. Electronic databases such as PubMed, Cochrane and EMBASE were searched from January 1, 2023 to March 31, 2023 to identify studies published in English language on hypofractionated RNI in post mastectomy patients. The search was carried out with the National Library of Medicine's Medical Subject Heading (MeSH) terms like "regional nodal irradiation," "hypofractionated" and "hypofractionation in breast cancer" with different Boolean operators (and/or). A manual search of reference lists of included articles was also performed to make sure there were no additional cases unidentified from the primary search. Studies deemed potentially eligible were identified and assessed by same independent reviewers to confirm eligibility. RNI data are mainly from a randomized study from Beijing and pooled data from START trials. There are also data from retrospective and single institutional studies and a few phase II studies with limited number of patients using different dose fractionations and techniques of radiotherapy. Doses used in these trials ranged from 26-47.7 Gy in 5-19 fractions over 1-4 weeks. Grade ≥ 2 pulmonary fibrosis and lymphedema rate ranged from 2%-7.9% and 3%-19.8% respectively. Grade ≥ 2 shoulder dysfunction and brachial plexopathy ranged from 0.2%-28% and 0%-< 1%, respectively. Late effects with a dose range of 26-40 Gy delivered in 5 to 15 fractions over 1-3 weeks were less/similar to conventional fraction. Current data showed lower/similar rates of toxicity with hypofractionated RNI compared with conventional fractionation RNI. Doses of 26 Gy to 40 Gy delivered in 5 to 15 fractions over 1-3 weeks are safe for RNI. With limited data, ultra-hypofractionation 26 Gy/5 fractions/1 week also seems to be safe. However, long-term outcome is awaited and many trials are going on to address its efficacy and safety.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma.

In this editorial I comment on the article, published in the current issue of the World Journal of Clinical Oncology. Primary central nervous system lymphoma (PCNSL) is a disease of elderly and immunocompromised patients. The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate (HD-MTX) until disease progression. They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients. They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL. PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities. Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant. Gradually, treatment of patients with PCNSL is going to become individualized.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial.

Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Challenges in commissioning the "TSET" technique: A new approach towards monitor unit calculation and beam profile measurements.

INTRODUCTION: Total skin electron beam therapy, commonly known as TSET, is a good choice of treatment for patients suffering from mycosis fungoides. The aim of this study was to introduce a new approach to the beam profile measurement using diodes and to calculate the monitor units required for the TSET treatment by the use of a simple setup of output measurement. Dosimetric measurements required for the treatment were taken to establish the Stanford technique in the department, and the measured data was compared with the published data. MATERIALS AND METHODS: High-energy Linear Accelerator Clinac-DHX, Varian medical system, Palo Alto, CA, was commissioned for TSET. The output of the machine was measured by the use of a Parallel-Plate Chamber (PPC40) as per the TRS 398 recommendation. Diode dosimeters (EDD2 and EDD5) were used for beam profile measurements due to easy setup and to reduce the measurement time. RESULTS: Homogeneous dose distribution within a field size of 80 cm x160 cm was observed with the variation of -5.0% on the horizontal axis and -5.4% on the vertical axis. The calculated monitor unit to deliver 200 cGy per fraction per field at the source to surface (SSD) of 416 cm was 489 MU. CONCLUSION: The technique described for the output measurements is simple and accurate. Results of the absorbed dose and MU measured were within good agreement compared to the published literature.

HYPofractionated Adjuvant RadioTherapy in 1 versus 2 weeks in high-risk patients with breast cancer (HYPART): a non-inferiority, open-label, phase III randomised trial.

BACKGROUND: Breast cancer is the most common cancer in women. Radiotherapy is an important part of breast cancer treatment after surgery. Breast cancer radiotherapy is usually delivered in 3-5 weeks. This is a long duration for women with breast cancer to stay away from the family and work. We wanted to reduce this duration so that the wages loss and the logistics can be minimised for these patients. Hypofractionation, i.e. high dose per fraction, is delivered in a smaller number of days. In this study, we will compare a 1-week schedule of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiotherapy against 2 weeks for locoregional disease control, toxicities, quality of life (QoL), survival and second cancers after primary surgery in patients with breast cancer. METHODS: Eligible patients with breast cancer after mastectomy or breast conserving surgery (BCS) will be treated with a radiotherapy dose of 26 Gy in 5 fractions over 1 week in the study arm and 34 Gy in 10 fractions over 2 weeks in the control arm. The primary endpoint of this noninferiority study will be locoregional tumour control. Secondary endpoints will be early and late radiation toxicities, quality of life, contralateral primary tumours, regional and distant metastases, survival and second cancers. A total of 1018 patients will be randomised (1:1) to receive 1 week or 2 weeks of radiotherapy. An event-driven analysis will be performed after at least 94 patients have documented locoregional recurrences. Acute radiation toxicity will be assessed and scaled according to the RTOG grading system. Late radiation toxicity will be assessed with the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer late radiation morbidity scale. Cosmetic assessment will be done using Harvard/NSABP/RTOG breast cosmesis grading scale at baseline and 3 and 5 years. QoL will be assessed with EORTC QLQ-30 and EORTC QLQ-BR 23 at baseline and 3 and 5 years. DISCUSSION: Hypofractionation reduces treatment time to half while maintaining breast cosmesis and gives control rates equal to conventional fractionation. This is possible because breast tissue can tolerate high dose per fraction. In this study, we presume that 1-week radiotherapy will be non-inferior to 2 week radiotherapy, i.e. disease control will be similar with both the schedules without additional side effects, and QoL of these patients will be maintained. If we are able to achieve these outcomes, then patients will be able to complete their radiotherapy in less duration. There is not much data on regional nodal irradiation with hypofraction in breast cancer. We have used hypofraction for regional nodal irradiation in the past and not encountered any safety issue. If we are able to prove that late-term effects are comparable in the two schedules, it will make the radiation oncologist confident about hypofractionation in breast cancer. As breast cancer is a leading cancer in females and radiation therapy is an integral part of its local management, hypofractionation will help radiation centres worldwide to meet the growing need for radiation treatment in breast cancer, particularly in developing countries where resources are limited. It will also reduce the financial burden on the patient and family. Since we will treat these patients with both simple and complex radiotherapy techniques, it will also be possible for the low-income countries to follow this trial without needing a high-end or expensive radiotherapy equipment as the planning and treatment process will be very simple. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov ID NCT04472845 and CTRI with REF/2020/09/037050.

Double-hit and double-expressor primary central nervous system lymphoma: Experience from North India of an infrequent but aggressive variant.

Background: High-grade non-Hodgkin B-cell lymphoma is an aggressive mature B-cell lymphoma that depicts poor treatment response and worse prognosis. The presence of MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements qualifies for triple-hit and double-hit lymphomas (THL/DHL), respectively. We attempted to explore the incidence, distribution, and clinical characteristics of the primary high-grade B-cell lymphoma of the central nervous system (CNS) in our cohort from North India. Methods: All the histologically confirmed cases of primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) over a period of 8 years were included. Cases showing MYC and BCL2 and/or BCL6 expression on immunohistochemistry (IHC) (double- or triple-expressor) were further analyzed by fluorescence in situ hybridization for MYC, BCL2 and /or BCL6 rearrangements. The results were correlated with other clinical and pathological parameters, and outcome. Results: Of total 117 cases of PCNS-DLBCL, there were seven (5.9%) cases of double/triple-expressor lymphomas (DEL/TEL) (six double- and one triple-expressor) with median age of 51 years (age range: 31-77 years) and slight female predilection. All were located supratentorially and were of non-geminal center B-cell phenotype. Only triple-expressor case (MYC+/BCL2+/BCL6+) demonstrated concurrent rearrangements for MYC and BCL6 genes indicating DHL (n = 1, 0.85%), while none of the double-expressors (n = 6) showed MYC, BCL2, or BCL6 rearrangements. The mean overall survival of the DEL/TEL was 48.2 days. Conclusion: DEL/TEL and DHL are uncommon in CNS; mostly located supratentorially and are associated with poor outcome. MYC, BCL2, and BCL6 IHC can be used as an effective screening strategy for ruling out double/ triple-expressor PCNS-DLBCLs.

Radiotherapy dose de-escalation in patients with high grade non-Hodgkin lymphoma in a real-world clinical practice.

PURPOSE: The standard treatment of non-Hodgkin lymphoma (NHL) comprises combined modality treatment, radiotherapy (RT), and chemotherapy with rituximab which has significantly improved both disease-free survival (DFS) and overall survival (OS). However, there is no uniformity in radiation dose usage in these patients. In this retrospective study, we compared lower radiation dose with higher in patients with aggressive NHL. MATERIALS AND METHODS: From 2007 to 2017, treatment records of all high-grade NHL or diffuse large B-cell lymphoma and non-central nervous system NHL were included. We compared response rates, OS and DFS of patients who received ≤30 Gy RT to those with >30 Gy. Univariate and multivariate analyses were done to determine factors affecting prognosis, i.e., age, sex, stage, International Prognostic Index (IPI), adding rituximab, and radiation dose. RESULTS: A total of 184 NHL patients treated with combined modality or radiation alone having complete follow-up details were analyzed. At median follow-up of 66.8 months, 5-year OS was 72.8% in high-dose group versus 69.9% in low-dose group (p = 0.772) and 5-year DFS 64.7% versus 64.1% (p = 0.871). Patients having early-stage disease receiving low dose and those with advanced disease treated with >30 Gy had better OS and DFS though not statistically significant. Adding rituximab was associated with significantly better OS and DFS irrespective of radiation dose delivered. High IPI score and omitting rituximab were the only factors that significantly worsened both OS and DFS. Acute radiation toxicities were comparable in both groups (p = 0.82). Among late toxicities, no patient developed a second malignancy and 5% died due to cardiovascular complications (p = 0.595) though only two patients (1.1%) had received thoracic radiation. CONCLUSION: The two groups had comparable response rates, acute toxicities, DFS and OS. This study suggests that RT dose reduction may be possible in high-grade NHL without compromising the DFS and OS.

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India.

Background: Young women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India. Materials and methods: Between January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35-40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method. Results: Of total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1-30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups. Conclusion: Young BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer.

Objective: Conservative approaches in muscle-invasive bladder cancer (MIBC) have been evolved to avoid aggressive surgery, but are limited to elderly, frail, and patients medically unfit for surgery. Our study aimed to assess the response rate of neoadjuvant chemotherapy (NACT) before radiotherapy (RT) in MIBC patients. Methods: Forty patients with urothelial carcinoma of stage T2-T4a, N0, M0 were enrolled between November 2013 and November 2015, and treated with three cycles of NACT with gemcitabine-cisplatin. Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients who achieved complete response (CR) and partial response (PR) >50% were treated with radical RT, and those who had PR <50%, stable disease (SD), and progressive disease (PD) underwent radical cystectomy (RC). Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model. Results: After NACT, 35 (87.5%) patients achieved either PR >50% or CR, and were treated with RT. Five (12.5%) patients who had PR <50%, SD, or PD underwent RC. All patients who received radiation showed CR after 6 weeks. Median follow-up was 43 months (range: 10-66 months) and median overall survival (OS) was not reached. Three-year OS, local control, and disease-free survival were 70.1%, 60.9%, 50.6%, respectively, and 50% of patients preserved their functioning bladder. Three-year OS rate was 88.9% in patients who achieved CR to NACT, 73.1% in patients with PR ≥50% and 40% in patients with PR <50%. Conclusion: NACT followed by RT provides a high probability of local response with bladder preservation in CR patients. Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

Accelerated hypofractionated breast radiotherapy with simultaneous integrated boost: a feasibility study.

PURPOSE: To assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer. MATERIALS AND METHODS: A total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves. RESULTS: The mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively. CONCLUSION: With this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population.

Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and the PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression in the PCNSL and evaluated their prognostic significance. All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1, and PD-L1 was performed on the tissue microarray. Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male-to-female ratio of 0.91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells were significantly associated with the longer OS (p = 0.037) and DFS (p = 0.023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not reach statistical significance (p > 0.05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p = 0.037). The TME plays a significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1-expressing immune cells is associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.

Role of gamma angle in treatment planning of vestibular schwannoma in Gamma Knife: A retrospective study.

Gamma angle plays a major role in Gamma Knife Radiosurgery (GKRS) treatment planning. Selecting an appropriate gamma angle may help in mitigating unnecessary radiation exposure to organs at risk (OARs). The aims in GKRS of vestibular schwannoma (VS) is to deliver sufficient radiation to the tumor extending into internal auditory canal (IAC) while keeping basal turn of cochlea and brain stem away from 4 and 12 Gy radiation exposure, respectively. This study analyses the optimal gamma angle in GKRS for VS treatment planning. The study was performed using old MRI datasets of 16 patients of VS in Leksell GammaPlan version 10.1.1. T2 weighted contrast MRIs were used for the planning purposes. Three different plans were made for each patient at gamma angles 90°, 110° and 70° using hybrid inverse planning technique. Dynamic shaping was used to achieve as low as reasonably achievable (ALARA) doses to the cochlea without compromising target coverage (i.e. coverage of more than 97% of tumor volume). This comparative analysis shows minimal radiation exposure to cochlea for plans made at gamma angle 110° compared to 90° and 70°. Average percentage volume of cochlea receiving 4 Gy were 9.63 ± 12.32%, 6.19 ± 8.24%, and 25.25 ± 31.82% at gamma angles 90°, 110° and 70°, respectively (one-way ANOVA p = 0.0247). The average selectivity indices were 83.44 ± 7.13, 84.06 ± 7.84 and 83.56 ± 7.22 at gamma angles 90°, 110° and 70° respectively. Similarly, the gradient indices and beam on time were 2.80 ± 0.23, 2.81 ± 0.23 and 2.80 ± 0.25 and 120.65 ± 59.63, 117.95 ± 58.06 and 123.99 ± 61.61 min, respectively, at 90°, 110° and 70°. The selectivity index, gradient index and beam on time were minimal at gamma angle 110° compared to the other two angles, but not statistically significant (one-way ANOVA p-values were 0.9686, 0.9942 and 0.9598, respectively). The gamma angle of 110° is a good choice for treatment planning of VS patient in Gamma Knife as it gives better treatment plans (minimal cochlea doses).

Breast cancer hypofractionated radiotherapy in 2-weeks with 2D technique: 5-year clinical outcomes of a phase 2 trial.

BACKGROUND: To report clinical outcomes and late toxicities of a 2-week hypofractionated post-operative loco-regional radiotherapy in patients with breast cancer. MATERIALS AND METHODS: This trial was approved by the Institutional Ethics Committee and registered with gov, no. NCT02460744. Between June 2013 and October 2014, 50 patients with breast cancer, post mastectomy or breast conserving surgery (BCS) were included in this study, of whom 10 had BCS. Patients were planned on a 2-dimentional (2D) simulator with 2 tangential fields and an incident supraclavicular field. Radiotherapy dose was 34 Gy/10#/2 weeks and a sequential boost of 10 Gy/5#/1 wk in BCS patients. The primary endpoint was the rate of acute skin toxicities previously reported. Here, we report the secondary end points of late toxicities, cosmesis, local recurrence, disease-free survival (DFS) and overall survival (OS). Late skin toxicities were recorded according to the Radiotherapy and Oncology Group (RTOG) scoring criteria. Cosmetic outcomes were assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG breast cosmesis and the Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) scales for the breast and chest wall, respectively. Kaplan-Meier estimates of DFS and OS were calculated, and 5-year DFS and OS rates (with approximate 95% CIs) were estimated. RESULTS: Late grade ≥ 2 chest wall induration, hypopigmentation and subcutaneous fibrosis were seen in 3 (6%), 3 (6%) and 1 (2%) patients, respectively. Chest wall cosmesis was excellent/good in 34 (72%) and fair/bad in 13 (28%) patients. In BCS patients, grade 2 skin induration, subcutaneous fibrosis and edema was observed in 1 patient (11%) each. Cosmesis was excellent/good in 7 (78%) and fair/bad in 2 (22%) patients. Late grade ≥ 2 arm edema, pain and shoulder stiffness were reported by 1 (2%), 2 (4%) and 2 (4%) patients, respectively. No local recurrences were observed. Five patients developed distant metastases (10%). Seven patients died (14%). The 5-year DFS and OS rate was 90% (95% CI: 77-96%) and 88% (95% CI: 75-94%), respectively. CONCLUSION: Hypofractionated radiotherapy in 2 weeks in patients with breast cancer was associated with minimal late toxicity, good cosmetic outcome and excellent local control. This trial may be of relevance for developing countries where resources are limited.

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

BACKGROUND: A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluate the prognostic factors associated with clinical outcomes. METHODS: Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. RESULTS: A total of 108 patients were identified with a median follow-up of 31.7 months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26 months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5 years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. CONCLUSION: The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.

Male breast cancer: Outcome with adjuvant treatment.

INTRODUCTION: Male breast cancer (MBC) incidence is <1%, but it is increasing. MBC incidence increases with age. There are no randomized trials on MBC because of low number of patients seen in any institution and hence its management is derived from breast cancer (BC) in women. In this study, we analyzed outcome in MBC patients with adjuvant treatment. MATERIALS AND METHODS: From 1991 to 2014, 81 men with BC were retrospectively analyzed for demographic, clinicopathological, and treatment outcomes. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. DFS and OS were estimated using Kaplan-Meier method and compared between patients receiving and not receiving adjuvant treatment using log-rank test. RESULTS: The median age was 57 years (range 30-86 years). Right, left, and bilateral BCs were seen in 41 (51%), 38 (47%), and 2 (2%) men, respectively. The mean duration of symptoms was 25 months (range 1-240 months). Comorbidity and family history was present in 31 (38%) and 3 (4%) men, respectively. The mean tumor size was 5 cm × 5 cm (range, 1 cm × 1 cm to 10 cm × 10 cm). Nipple was involved in 46 (57%) men. Early, locally advanced, and metastatic disease were seen in ??30 (37%), 34 (42%), and 17 (21%) men, respectively. Majority (71, 88%) of men had invasive ductal carcinoma histology. In radically treated 64 men, neoadjuvant chemotherapy was given to 12 (19%) patients (fluorouracil, adriamycin, and cyclophosphamide [FAC] to 9 and FAC + taxanes to 3), with CR in 4 (33.3%) and partial response (PR) in 8 (66.7%) patients. Mastectomy was done in 55 (86%) and wide local excision in 9 (14%) men. Margins and nodes were positive in 17 (27%) and 38 (59%) men, respectively. Estrogen receptor, PR, and human epidermal growth factor receptor 2/neu positive were seen in 27 (42%), 17 (26.5%), and 2 (3%) patients, respectively. Adjuvant hypofractionated radiotherapy, chemotherapy, and tamoxifen were received by 51 (80%), 35 (55%), and 45 (70%) men, respectively. Median follow-up was 60 months (range 4-278 months). Locoregional recurrence occurred in 8 (12.5%) and distant metastasis in 22 (34%) men, respectively. DFS and OS at 10 years were 42% and 53%, respectively. DFS and OS were significantly better in men with adjuvant radiation (54% vs. 24%, P = 0.007 and 57% vs. 35%, P = 0.022, respectively) and hormonal therapy (57% vs. 14.5%, P = 0.004 and 62% vs. 39%, P = 0.045, respectively). Chemotherapy had no impact on DFS and OS. CONCLUSION: Adjuvant hypofractionated radiotherapy and hormonal therapy significantly improved DFS and OS in MBC patients. Chemotherapy had no impact on DFS and OS.

Comparison of two radiation boost schedules in postlumpectomy patients with breast cancer.

BACKGROUND: We have been practicing hypofractionation, 40 Gy in 16 fractions over 3 weeks for whole breast irradiation (WBI) for the past five decades with or without boost at our center. In this study, we compared two boost schedules of 10 Gy/5#/1 week with 16 Gy/8#/1.5 weeks in postlumpectomy patients with breast cancer after WBI. MATERIALS AND METHODS: From June 2012 to June 2016, the study included 87 breast cancer patients postbreast conservation surgery. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. CT02142907). All patients were treated with WBI of 40 Gy/16#/3 weeks. WBI was followed by tumor bed boost of 10 Gy/5#/1 week in 44 patients and 16 Gy/8#/1.5 weeks in 43 patients, either with electron beam therapy or 3D CRT with photons. The primary endpoint of the study was the comparison of local control between two schedules. Secondary endpoints were acute and late radiation toxicities, cosmetic score analysis, disease-free survival (DFS), and overall survival (OS). The assessment of acute and late skin toxicity was made as per RTOG scores and LENT-SOMA scale. The cosmetic assessment was made with Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. RESULTS: Median follow-up was 55 months (range 18-78 months). Local recurrence was seen in 1 (2.3%) patient in the 16 Gy boost only. Acute Grade 2 skin toxicity was 33% in 16 Gy boost arm compared to 23% in 10 Gy boost arm. Late skin toxicities were also high in patients with 16 Gy boost. Grade ≥2 induration was seen in 4.5% and 14% of patients with 10 Gy and 16 Gy boost, respectively. None of the patients with 10 Gy boost had Grade 2 edema as compared to 5% with 16 Gy. Pigmentation was observed in 9% and 23% patients with 10 Gy and 16 Gy boost, respectively. Grade 1 fibrosis was 2% versus 12% in patients with 10 Gy and 16 Gy boost, respectively. The cosmetic score was good/excellent in 91% and 84% of patients with 10 Gy and 16 Gy boost, respectively. Distant metastasis occurred in 2 (4%) and 3 (7%) patients in 10 Gy and 16 Gy boost, respectively. DFS and OS at 5 years were comparable between the two boost schedules. CONCLUSION: Local control was comparable with 10 Gy and 16 Gy boost. Acute and late skin toxicities were higher with 16 Gy boost dose. The cosmetic score was better with 10 Gy boost. DFS and OS was comparable with the two boost schedules. Hence, a boost of 10 Gy/5# after WBI may be adequate in patients with breast cancer.

Clinicopathological features of primary central nervous system diffuse large B cell lymphoma: Experience from a Tertiary Center in North India.

BACKGROUND: Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare extra-nodal Non-Hodgkin lymphoma. There is relative paucity of literature on PCNSL from Indian subcontinent. We aimed to analyze the clinicopathological features of PCNSL and categorize them into germinal center B cell (GCB) and non-GCB subtypes to assess their prognostic significance in Indian context. METHODS: All patients with histopathologically diagnosed PCNSLs at our center over a period of 6 years were recruited and classified into GCB and non-GCB using Han's algorithm (immunohistochemistry for CD10, BCL6 and MUM1). In situ hybridization (ISH) for Epstein-Barr virus (EBV)-encoded RNA was performed. RESULTS: Eighty-six cases of PCNS-DLBCL were included with median age of 55 years. Majority of them were supratentorial in location (n = 62). All patients were immunocompetent. On immunohistochemical assessment, 69 (80.2%) were of NGCB subtype, 10 (11.6%) were of GCB subtype, and 7 (8.1%) were unclassified. Overall, MUM1, BCL-6, and CD10 expressions were seen in 69 (80.2%), 28 (32.6%), and 2 cases (2.3%), respectively. Four cases (4.6%) showed C-MYC expression. The median overall survival (OS) was 675 days. None of the factors (age, sex, location, immunomarkers, and GCB vs. NGCB phenotype) showed correlation with OS; however, BCL6 positive cases showed slight better OS (P > 0.05). All cases were negative for EBV-LMP1 on ISH. CONCLUSION: The majority of the CNS DLBCL belongs to non-GCB phenotype and uniformly carry poor prognosis, irrespective of their phenotype. Individual markers, such as BCL-6, MUM1, or CD10, are unable to predict outcome in PCNS-DLBCL.

Primary mediastinal germ cell tumors: Survival outcomes and prognostic factors - 10 years experience from a tertiary care institute.

Primary Mediastinal Germ Cell Tumor (PMGCT) is a rare and heterogeneous entity. These tumors are typically diagnosed in young adults and carry a poor prognosis. We conducted this study to evaluate the role of radiotherapy on treatment outcomes and prognostic factors in PMGCT that may allow a more adapted treatment strategy to improve survival. Case records of patients who presented with PMGCT over a period of 10-years from January-2009 to December-2019 were retrospectively evaluated. Survival analyses were calculated using Kaplan-Meier (Log-rank) method. Poor prognostic factors for survival were evaluated with Multivariate analysis using Cox-regression method. A total of 46-patients data was analyzed, the majority of the patients were males (95.7%) with a median age of 25-years (range, 17-62). Non-seminomatous histology was predominant (60.9%). Sixteen-patients (34.7%) presented with complications at their initial presentation. Majority of the patients were treated with multimodality approach using chemotherapy, surgery, and/or radiotherapy. At a median follow-up of 40.8 months, the 1, 3, and 5-year overall survival (OS) was 69.6%, 52.2%, and 44.7% respectively. Patients who received radiotherapy in first-line treatment showed significant improvement in 5-year OS (72% vs 30%, p = 0.004) and disease-free survival (70% vs 24%, p = 0.007) in comparison with patients who did not receive. Multivariate analysis revealed that radiotherapy, chemotherapy, surgery, and complications at presentation were independent prognostic factors for OS. PMGCTs are aggressive neoplasms especially in patients presenting with disease-related complications. Dual modality management (radiotherapy as local therapy along with chemotherapy) had shown improvement in survival.

Late-term effects of hypofractionated chest wall and regional nodal radiotherapy with two-dimensional technique in patients with breast cancer.

PURPOSE: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. METHODS: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at dmax and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). RESULTS: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. CONCLUSION: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. XXXX).