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.

Periprosthetic metastases in carcinoma of unknown primary: A rare association.

ABSTRACT: Septic or aseptic loosening may cause bone loss around artificial prosthesis leading to prosthesis failure. This occurrence due to metastatic infiltration of bone or surrounding soft tissues is rare but has been occasionally reported. We report a case of an elderly lady presenting with swelling and pain at the site of previous hemiarthroplasty performed for traumatic injury. On evaluation, she was found to have a lytic femur lesion with a large soft-tissue component around the prosthetic joint. Biopsy suggested a metastatic carcinoma of renal origin, but screening of kidneys did not reveal any primary lesion. She had additional skeletal metastatic lesions but no other primary site was detected either. She was given palliative radiotherapy and systemic therapy (sunitinib) based on the histologic diagnosis of renal cell origin but did not tolerate it. Thereafter, she is continuing on zoledronate every 4 weeks and best supportive management since 4 months from diagnosis.

Solitary fibrous tumor of the seminal vesicle.

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms with variable clinical behavior depending on age, tumor site, and size, and pathologic factors such as mitoses and necrosis. Imaging features on computed tomography (CT) or magnetic resonance imaging (MRI) are not specific, and the diagnosis relies on histopathology with immunohistochemistry. SFTs arising from seminal vesicles is rare and reported in only eight earlier cases. We discuss the clinical, histopathologic and positron emission tomography (PET) imaging characteristics of a 54-year-old patient with SFT of the seminal vesicle. The patient was treated with robot-assisted seminal vesiculotomy and is doing well on follow-up at two years.

[177Lu]Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial.

The prostate-specific membrane antigen (PSMA) inhibitor [177Lu]Lu-PSMA-617 has been previously demonstrated to be noninferior to docetaxel in achieving a biochemical response in chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Here, we report the final analysis of overall survival (OS) for a phase 2 randomized, controlled trial. Methods: Forty chemotherapy-naïve, PSMA-positive metastatic castration-resistant prostate cancer patients were randomly assigned to [177Lu]Lu-PSMA-617 (n = 20) or docetaxel (n = 20). Thirty-five patients received treatment per the protocol. Survival analysis was done using Kaplan-Meier curves and the Cox regression model. Results: The mean follow-up duration was 33.4 mo. In intention-to-treat analysis, the median OS for the [177Lu]Lu-PSMA-617 and docetaxel arms was 15.0 mo (95% CI, 9.5-20.5 mo) and 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.905). In per-protocol analysis, the median OS was 19.0 mo (95% CI, 12.3-25.7 mo) versus 15.0 mo (95% CI, 8.1-21.9 mo), respectively (P = 0.712). No significant difference in OS was observed between the 2 arms across the analyzed subgroups. Conclusion: Long-term outcomes with [177Lu]Lu-PSMA-617 administered earlier in the prechemotherapy setting are comparable to those with docetaxel.

Delineating and sparing the ileal conduit in adjuvant radiotherapy for bladder cancer with modulated radiotherapy.

Purpose: We undertook a prospective planning study to describe the delineation of ileal conduit (IC) loop on radiotherapy planning computed tomography (RTP CT) scan as an organ at risk (OAR) and its sparing using volumetric modulated arc therapy (VMAT) during adjuvant irradiation of bladder malignancies. Materials and Methods: Fifteen patients with bladder malignancy needing adjuvant radiotherapy postoperatively and having normal renal function underwent delayed phase RTP CT from June 2020 to March 2021, with certain modifications (Foley's catheter through stoma, additional delayed scans). We identified the course of ureters, external stoma, IC, and uretero-ileal (right and left) anastomotic sites. VMAT plans were generated. Results: A step-by-step description is given. Genitourinary OARs include kidneys, ureters, uretero-ileal anastomoses, and IC. The contrast on delayed scan opacifies ureters and IC. IC can be seen three-dimensionally as a structure with two fixed ends (blind proximal end anterior to the right sacroiliac joint and the open distal end over the right anterior abdominal wall in parasagittal location) and a 15-20 cm hanging intraabdominal loop that lies adjacent to the right iliac vessels. For prescription doses (PD) of 50.4 gray and 54 gray, respectively, VMAT plan achieved IC dose maximum to less than PD and V50 lower than 10 cc. Stoma sparing traditionally used as a surrogate for IC sparing is insufficient due to the variable intraabdominal location of IC loop. Conclusions: Delineation of IC as an OAR is feasible with slight modifications in the RTP protocols. VMAT (or other forms of intensity modulated radiation therapy) can help IC sparing and should be considered when it lies in close proximity to target volumes and the risk of additional morbidity is considerable.

Profile of 193 pediatric cancer patients managed with radiation therapy: Challenges and lessons learned.

Background: Series on radiotherapy (RT) practice in pediatric malignancies are limited in India as only a few centers practice pediatric RT, particularly under anesthesia. We aimed to study the clinical profile of pediatric cancer patients treated with RT and to analyze various challenges in pediatric RT under anesthesia. Materials and Methods: The data were prospectively maintained in Microsoft Excel spreadsheets. Pediatric cancer patients aged 0-14 years, registered in the RT department between February 1, 2019 and July 30, 2021were analyzed. Results: A total of 193 pediatric cancer patients (noncentral nervous system) received RT during the said period. Median age at presentation was 5.2 years (range: 9 months to 14 years) with a male-to-female ratio of 1.8:1. The majority of the patients were in the age group of 0-4 years (52.8%) followed by 5-9 years (29.5%) and ≥10 years (17.6%). Most common indications for RT included bone and soft-tissue tumors, retinoblastoma, Wilms tumor, neuroblastoma, and hematological malignancies. One hundred and seventy-nine (92.7%) patients received RT with curative intent, while 14 (7.3%) patients received palliative RT. Thirty (15.5%) patients needed anesthesia for RT. Ten (5.18%) patients required RT interruption due to toxicities with a median gap of 3 days. Conclusions: RT is challenging yet an important aspect of multidisciplinary care in paediatric cancers. Estimating the burden of pediatric patients in the RT department may help in assessing unmet needs, resource development, and prioritization, which may improve the cure rates.

Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma - A 13-years experience from a tertiary care centre.

Purpose: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival. Methods: A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant. Results: The median age of patients was 37.5 years (range, 5-72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse. Conclusion: ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.

Diagrammatic Approach to Delineate Phrenic Nerve in Central Lung Tumors.

Incremental use of high-dose radiation therapy (RT) with SABR in thoracic tumors has led to identification of many unusual toxicities (chest wall pain, rib fractures, vascular perforation, brachial plexopathy) and consequently additional organs at risk (OARs; chest wall, ribs, bronchial wall, carotid artery, brachial plexus). Phrenic nerve is another structure that may be affected at any point during its long course from origin until end, although symptomatic toxicities have been reported rarely in the setting of reirradiation, large-volume irradiation such as mantle field, or SABR. We undertook a prospective study to describe the delineation of phrenic nerve course on RT planning computed tomography scan as an OAR. An anonymized RT planning computed tomography scan of neck and thorax (1.5-mm slice thickness, intravenous contrast) was used for the study. Radiology textbooks and publications were reviewed, and the course was delineated with the help of 2 radiologists and 6 radiation oncologists well versed with thoracic radiologic anatomy. A step-by-step description in the form of a pictorial essay is given. The adjacent structures including cervical vertebrae, cervical and mediastinal vessels, lungs, heart, and so on were identified, and the course of phrenic nerve on either side is described in relation to these structures. Delineation of the phrenic nerve as an OAR is challenging but feasible. We recommend routine delineation of the phrenic nerve as an OAR during thoracic RT. Although specific dose constraints are not known yet, unnecessary dose to the same during RT planning should be minimized.

Temozolomide-induced vitiligo-like reaction: An extremely rare phenomenon.

ABSTRACT: Temozolomide (TMZ) is an alkylating chemotherapeutic drug, often used in high-grade glioma and metastatic melanoma. Common side effects of this include myelosuppression and gastrointestinal side effects. Vitiligo-like reaction is extremely rare after TMZ. Here, we report a case of a 55-year-old patient of glioblastoma who developed vitiligo-like reaction after starting adjuvant TMZ.

Mucoepidermoid carcinoma of the trachea in a 9-year-old male child: case report and review of literature.

Mucoepidermoid carcinoma (MEC) is most common malignancy of minor salivary glands in adults. Pulmonary MEC is extremely uncommon comprising of only 0.1%-0.2% of the primary lung malignancies and <1% of primary bronchial tumors. It is even rarer in children and literature limited to few case reports only. Here we present a case report of a 9-year-old boy diagnosed with primary MEC of trachea along with review of the literature. A 9-year-old male child presented with complaint of dry cough for two years which was later associated with shortness of breath after one year. Bronchoscopic examination revealed a growth arising from right lateral wall of carina occluding 50% of the lumen and detailed histopathological examination revealed it to be a MEC of the trachea. Patient underwent local excision of the tumor with primary anastomosis. In view of positive margins adjuvant radiotherapy of 60 Gy in 30 fractions were given to the tumor bed. Patient tolerated the treatment well and is disease free at 6 months follow-up. Experience with MEC of the trachea in children is limited and optimal treatment protocols have not been defined, with current treatment mainly extrapolated from MEC of the salivary glands.

Role of intraluminal brachytherapy in palliation of biliary obstruction in cholangiocarcinoma: A brief review.

Surgery is the only curative treatment for cholangiocarcinoma. However, most patients present with advanced disease, and hence are unresectable. Thus, the intent of treatment shifts from curative to palliative in the majority of cases. Biliary drainage with intraluminal brachytherapy is an effective means of relieving the malignant biliary obstruction. In this review, we discuss the role of brachytherapy in the palliation of obstructive symptoms in extrahepatic cholangiocarcinoma.

Managing brain tumors in pregnancy: The oncologist's struggle with maternal-fetal conflict.

The diagnosis of malignancy, particularly brain tumors, in pregnancy is uncommon but poses a complex dilemma for the management of both the patient and her fetus, as the interplay of disease with the physiological state of pregnancy affects both outcomes. The routine evaluations (symptomatology, imaging, and hormonal assessments) and treatments (surgery, radiation therapy, and chemotherapy) that are commonplace in brain tumor management may need to be omitted or modified keeping in mind the risk to offspring. Multidisciplinary care and extensive prenatal and perinatal counseling and monitoring are essential. In this review, we discuss the available data addressing these issues and factors which may affect considerations of therapeutic abortions, changes in surgical or medical practices, and outcomes thereof.

Small bowel adenocarcinoma: An overview.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract. However, these tumors are among those with worst prognosis. Vague clinical signs and symptoms and radiological diagnostic challenges often delay treatment, which negatively impacts the prognosis of the patients. However, recent advances in imaging technology, like multidetector computed tomography, magnetic resonance imaging, and capsule endoscopy, have made earlier and accurate diagnosis possible. Surgery is the treatment of choice followed by adjuvant therapy. However, there are no strict treatment guidelines available for the management of SBA. Most of the available evidence from colorectal and gastric carcinoma has been extrapolated to adequately manage SBA. Prognosis for SBA is better than gastric carcinoma but worse than colorectal carcinoma. Currently, there is not enough information on the molecular characteristics and tumor pathogenesis. Because the incidence of SBA is very low, there is a need for further studies to evaluate the possible application of newer investigative agents and strategies to obtain a better outcome within the framework of international collaborations.

Nandrolone-Induced Tumor Progression in Hormone-Sensitive Prostate Cancer.

ABSTRACT: Hormone-sensitive prostate cancer responds favorably to testosterone suppression induced by GnRH analogs or antagonists. This effect may theoretically be countered by anabolic steroids. We describe a patient of a recurrent hormone-sensitive prostate cancer who was on salvage androgen deprivation therapy with degarelix and developed rapid progression after over-the-counter nandrolone injections.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.

Nidus delineation and dosimetric comparison in arteriovenous malformation in stereotactic radiosurgery by using MRI and 3DCT angiography.

Purpose/Objectives: Accurate delineation of target is key to any successful radiosurgery. C-arm Dyna CT/ 3DCT angiography (3DCTA) has the potential of improving the accuracy of nidus delineation in intracranial arteriovenous malformations (AVM) due to high temporo-spatial resolution of vessel architecture. Here, we present a comparison of nidus delineation and dosimetric parameters between digital 3DCTA and MRI. Materials/Methods: Ten consecutive patients treated for intracranial AVMs were included in this study. All patients underwent MRI/MRA, and 3DCTA and all images were co-registered. AVM were delineated using 3DCTA (GTV3DCTA) and contrast enhanced MRI/MRA (GTVMRI). Hausdorff distance (HD) matrices and dice similarity coefficient (DSC) matrices were analysed. Stereotactic radiosurgery plans were developed for both the volumes for all patients and statistical analysis were performed with T-test. Results: Mean volumes of GTV3DCTA and GTVMRI were 1.771 cc (SD 1.794cc, range 0.124-4.191cc) and 2.183cc (SD 2.16cc, range 0.221-6.133cc), respectively. Significant deviation (p=0.018) was found when taking GTVMRI as a primary and comparing it to GTV3DCTA (MD=0.723cc±0.816cc). Similar result was observed with GTV3DCTA as primary and GTVMRI as secondary (MD=0.188cc, SD=0.193cc, p=0.024). Maximum HD was in the range of 1.71 to 7.44mm (mean=4.27mm, SD=1.56). For GTV3DCTA based plans, significant deviation was found between GTVMRI and GTV3DCTA in dose coverage and the mean difference was 22.17% (SD 16.73). In GTVMRI based plans, the mean CIRTOG deteriorated from 1.33 to 2.18 for GTVMRI and GTV3DCTA, respectively. Significant deviation was found in CIRTOG (0.005) and mean deviation was 0.86(SD=0.72) when comparing GTVMRI and GTV3DCTA. Highly significant (p=0.002) deviation was found in CIPaddick between GTVMRI and GTV3DCTA for GTVMRI based plans with mean difference of 0.26(SD=0.4, for GTVMRI=0.3, GTV3DCTA=0.46). Conclusion: Nidus volume was significantly altered with the use of 3DCTA compared to that of MRA/MRI images. Multimodality imaging is crucial for accurate target delineation, and successful radiosurgical obliteration of nidus.