Translation and Pilot Validation of Hindi, Marathi, and Bangla Translation of Quality-of-Life EORTC Radiation Proctitis Module (PRT-20) for Routine Clinical Use.

Rahul Krishnatry The aim of this study was to translate and validate the European Organization for Research and Treatment for Cancer (EORTC) "Radiation Proctitis" (PRT-20) module in Hindi, Marathi, and Bangla languages. The EORTC PRT-20 was translated into Hindi, Marathi, and Bangla using EORTC guidelines. Two separate translators first translated the original questionnaire into the three regional languages, following which a reconciled forward translation was compiled. This reconciled version in each language was then back-translated into English by two other translators. This back-translated version was then compared with the original the EORTC questionnaire for correctness, and the preliminary questionnaires were formed in all three languages. The EORTC translation unit approved the questionnaires. The preliminary questionnaires were administered to 30 patients (10 for each language) diagnosed with rectal or anal canal cancer who had received pelvic radiotherapy and were at risk of developing PRT. None of the patients had seen the questionnaire before. After filling out the questionnaire, each patient was interviewed for difficulty in answering, confusion, understanding, or if any of the questions were upsetting and if patients would have asked the question differently. No changes were suggested for Marathi and Bangla translations. Two modifications were suggested in the Hindi translation, which was then retested in five patients and finalized. All the suggestions were incorporated into the preliminary questionnaires, which were sent back to the EORTC for final approval. After reviewing the entire report of pilot testing for the translated quality-of-life questionaire-PRT-20 in three languages, it was approved by the EORTC translation unit. The translated questionnaires were reliable, with Cronbach α values of 0.767, 0.799, and 0.898 for Hindi, Marathi, and Bangla, respectively. The Hindi, Marathi, and Bangla translations of PRT-20 have been approved by the EORTC and can be used in routine clinical practice.

Deep inspiratory breath-hold radiotherapy on a Helical Tomotherapy unit: Workflow and early outcomes in patients with left-sided breast cancer.

Introduction: The clinical implementation of deep inspiratory breath-hold (DIBH) radiotherapy to reduce cardiac exposure in patients with left-sided breast cancer is challenging with helical tomotherapy(HT) and has received little attention. We describe our novel approach to DIBH irradiation in HT using a specially designed frame and manual gating, and compare cardiac substructure doses with the free-breathing (FB) technique. Material and methods: The workflow incorporates staggered junctions and a frame that provides tactile feedback to the patient and monitoring for manual cut-off. The treatment parameters and clinical outcome of 20 patients with left-sided breast cancer who have undergone DIBH radiotherapy as a part of an ongoing prospective registry are reported. All patients underwent CT scans in Free Breathing (FB) and DIBH using the in-house Respiframe, which incorporates a tactile feedback-based system with an indicator pencil. Plans compared target coverage, cardiac doses, synchronizing treatment with breath-hold and avoiding junction repetition. MVCT scans are used for patient alignment. Results: The mean dose (Dmean) to the heart was reduced by an average of 34 % in DIBH-HT compared to FB-HT plans (3.8 Gy vs 5.7 Gy). Similarly, 32 % and 67.8 % dose reduction were noted in the maximum dose (D0.02 cc) of the left anterior descending artery, mean 12.3 Gy vs 18.1 Gy, and mean left ventricle V5Gy 13.2 % vs 41.1 %, respectively. The mean treatment duration was 451.5 sec with a median 8 breath-holds; 3 % junction locations between successive breath-holds were replicated. No locoregional or distant recurrences were observed in the 9-month median follow-up. Conclusion: Our workflow for DIBH with Helical-Tomotherapy addresses patient safety, treatment precision and challenges specific to this treatment unit. The workflow prevents junction issues by varying daily breath-hold durations and avoiding junction locations, providing a practical solution for left-sided breast cancer treatment with HT.

Translation and pilot validation of Hindi, Marathi, and Bangla translation of quality of life EORTC module (QLQ-SH-22) for assessing sexual health-related quality of life.

AIM: To translate and validate the European Organization for Research and Treatment for Cancer (EORTC) module for assessing the sexual health-related quality of life in cancer patients (QLQ-SH22), in Hindi, Marathi, and Bangla languages for clinical use. METHODS AND RESULTS: The EORTC QLQ-SH-22 was translated into Hindi, Marathi, and Bangla by adopting standard guidelines given by EORTC. Initially, the original questionnaire was forward translated by two separate translators, followed by the reconciliation of the forward translations by a third person. This was followed by two back translations of the reconciled version into English by two other translators. These back-translated questions were then compared with the original EORTC questions for accuracy, and once acceptable, a preliminary questionnaire was prepared in all three languages. These questionnaires were then pilot tested with 30 patients (10 for each language) diagnosed with any of the cancers in the pelvic region who are expected to be at risk of sexual quality of life due to tumor or treatment like pelvic radiotherapy. Participated patients had never seen or filled the questionnaire before, each patient was interviewed after filling the questionnaire for difficulty in answering, confusion, difficulty understanding, or if any of the questions were upsetting and if patients would have asked the question differently. RESULTS: None of the patients reported any changes or suggestions for all the three translations. All the translated questionnaires were well understood by all the patients. Pilot testing reports were sent to EORTC. After reviewing the entire report of Hindi, Marathi, and Bangla translations, these questionnaires were approved by the EORTC translation unit. The questionnaires are reliable with Cronbach's α for Hindi, Marathi, and Bangla being 0.69, 0.66, and 0.86, respectively. CONCLUSION: The final Hindi, Marathi, and Bangla translations of SH 22 have been approved by the EORTC and can be used to assess the sexual health of cancer patients in routine oncology practices and/or clinical studies.

Combinatorial approach of immuno-proton therapy in cancer: Rationale and potential impact.

Cancer management is an expansive, growing, and evolving field. In the last decade or so, immunotherapy (IT) and particle beam therapy have made a tremendous impact in this domain. IT has already established itself as the fourth pillar of oncology. Recent emphasis has been centred around combination therapy, postulating additive or multiplicative effects of combining IT with one or more of the three conventional "pillars," that is, surgery, chemotherapy, and radiotherapy. Radio-IT is being increasingly explored and has shown promising outcomes in both preclinical and clinical settings. Particle beam therapy such as protons, when used as the radiotherapeutic modality in conjunction with IT, can potentially limit toxicities and improve this synergism further. Modern proton therapy has demonstrated a reduction in integral dose of radiation and radiation-induced lymphopenia in various sites. Protons, by virtue of their inherent clinically desirable physical and biological characteristics, namely, high linear energy transfer, relative biological effectiveness of range 1.1-1.6, and proven anti-metastatic and immunogenic potential in preclinical studies, might have a superior immunogenic profile than photons. Proton-IT combination is being studied currently by various groups in lung , head neck and brain tumors, and should be evaluated further in other subsites to replicate preclinical outcomes in a clinical setting. In this review, we summarize the currently available evidence for combinatorial approaches and feasibility of proton and IT combination, and thereafter highlight the emerging challenges for practical application of the same in clinics, while also proposing plausible solutions.

Successful Implementation of Image-Guided Pencil-Beam Scanning Proton Therapy in Medulloblastomas.

Medulloblastoma is the most common malignant brain tumour in children, while much rarer in adults. Although the prognosis and outcomes have greatly improved in the era of modern multidisciplinary management, long-term treatment-induced toxicities are common. Craniospinal irradiation followed by a boost to the primary and metastatic tumour sites forms the backbone of treatment. Proton therapy has been endorsed over conventional photon-based radiotherapy due to its superior dosimetric advantages and subsequently lower incidence and severity of toxicities. We report here our experience from South-East Asia's first proton therapy centre of treating 40 patients with medulloblastoma (38 children and adolescents, 2 adults) who received image-guided, intensity-modulated proton therapy with pencil-beam scanning between 2019 and 2023, with a focus on dosimetry, acute toxicities, and early survival outcomes. All patients could complete the planned course of proton therapy, with mostly mild acute toxicities that were manageable on an outpatient basis. Haematological toxicity was not dose-limiting and did not prolong the overall treatment time. Preliminary data on early outcomes including overall survival and disease-free survival are encouraging, although a longer follow-up and data on long-term toxicities are needed.

Proton therapy and oral mucositis in oral & oropharyngeal cancers: outcomes, dosimetric and NTCP benefit.

INTRODUCTION: Radiation-induced oral mucositis (RIOM), is a common, debilitating, acute side effect of radiotherapy for oral cavity (OC) and oropharyngeal (OPx) cancers; technical innovations for reducing it are seldom discussed. Intensity-modulated-proton-therapy (IMPT) has been reported extensively for treating OPx cancers, and less frequently for OC cancers. We aim to quantify the reduction in the likelihood of RIOM in treating these 2 subsites with IMPT compared to Helical Tomotherapy. MATERIAL AND METHODS: We report acute toxicities and early outcomes of 22 consecutive patients with OC and OPx cancers treated with IMPT, and compare the dosimetry and normal tissue complication probability (NTCP) of ≥ grade 3 mucositis for IMPT and HT. RESULTS: Twenty two patients, 77% males, 41% elderly and 73% OC subsite, were reviewed. With comparable target coverage, IMPT significantly reduced the mean dose and D32, D39, D45, and D50, for both the oral mucosa (OM) and spared oral mucosa (sOM). With IMPT, there was a 7% absolute and 16.5% relative reduction in NTCP for grade 3 mucositis for OM, compared to HT. IMPT further reduced NTCP for sOM, and the benefit was maintained in OC, OPx subsites and elderly subgroup. Acute toxicities, grade III dermatitis and mucositis, were noted in 50% and 45.5% patients, respectively, while 22.7% patients had grade 3 dysphagia. Compared with published data, the hospital admission rate, median weight loss, feeding tube insertion, unplanned treatment gaps were lower with IMPT. At a median follow-up of 15 months, 81.8% were alive; 72.7%, alive without disease and 9%, alive with disease. CONCLUSION: The dosimetric benefit of IMPT translates into NTCP reduction for grade 3 mucositis compared to Helical Tomotherapy for OPx and OC cancers and encourages the use of IMPT in their management.

IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis.

Radiation dermatitis is a major concern in intensity modulated proton therapy (IMPT) for head and neck cancer (HNC) despite its demonstrated superiority over contemporary photon radiotherapy. In this study, dose surface histogram data extracted from forty-four patients of HNC treated with IMPT was used to predict the normal tissue complication probability (NTCP) of skin. Grades of NTCP-skin were clustered using the K-means clustering unsupervised machine learning (ML) algorithm. A new skin-sparing IMPT (IMPT-SS) planning strategy was developed with three major changes and prospectively implemented in twenty HNC patients. Across skin surfaces exposed from 10 (S10) to 70 (S70) GyRBE, the skin's NTCP demonstrated the strongest associations with S50 and S40 GyRBE (0.95 and 0.94). The increase in the NTCP of skin per unit GyRBE is 0.568 for skin exposed to 50 GyRBE as compared to 0.418 for 40 GyRBE. Three distinct clusters were formed, with 41% of patients in G1, 32% in G2, and 27% in G3. The average (± SD) generalised equivalent uniform dose for G1, G2, and G3 clusters was 26.54 ± 6.75, 38.73 ± 1.80, and 45.67 ± 2.20 GyRBE. The corresponding NTCP (%) were 4.97 ± 5.12, 48.12 ± 12.72 and 87.28 ± 7.73 respectively. In comparison to IMPT, new IMPT-SS plans significantly (P < 0.01) reduced SX GyRBE, gEUD, and associated NTCP-skin while maintaining identical dose volume indices for target and other organs at risk. The mean NTCP-skin value for IMPT-SS was 34% lower than that of IMPT. The dose to skin in patients treated prospectively for HNC was reduced by including gEUD for an acceptable radiation dermatitis determined from the local patient population using an unsupervised MLA in the spot map optimization of a new IMPT planning technique. However, the clinical finding of acute skin toxicity must also be related to the observed reduction in skin dose.

Robustly optimized hybrid intensity-modulated proton therapy for craniospinal irradiation.

Aim: The aim of the study was to investigate the hybrid robust optimization planning approach in intensity-modulated proton therapy (IMPT) of craniospinal irradiation (CSI). Subjects and Methods: Five IMPT-based adult CSI plans in supine position were created using Raystation treatment planning system (TPS) modelled for Proteus plus proton therapy system. A hybrid planning strategy was implemented, where clinical target volume was robustly optimized (RB) for set up uncertainties and planning target volume was optimized for target coverage using minimax algorithm in the TPS. Beam angle selection, optimization, and dose calculation approach were carefully performed to ensure optimum organ at risk (OAR) sparing, even with potential setup and range errors. The complementary dose gradients in junctions were generated using spot assignment and RB technique. Dosimetric outcomes in both nominal plan and the 16 error scenarios (±3 mm setup and 3.5% range) were analyzed using standard dose volume histogram. Results: This planning approach resulted in a homogeneous dose distribution in the target volume of CSI, including the junction regions, by explicitly reducing number of robust optimization scenarios. The proposed technique was also able to achieve excellent coverage to cribriform plate with lower lens doses and minimal dose to other OARs. Target and OAR doses in the nominal plans as well as in the worst case scenarios with setup and range errors were able to meet the predefined clinical goal. Conclusions: This proposed planning technique is efficient, robust against the uncertainties. It could be adopted in other proton therapy centers.

Standard Operating Procedure (SOP) for mould room practices and simulation of head neck cancer patients undergoing proton therapy.

Head Neck cancer patients treated with modern proton therapy need special attention during mould room procedures. In addition to usual mould room practices, patients undergoing Intensity Modulated Proton Therapy (IMPT) require attention to the special characteristics of protons viz., sensitivity to beam path and its alteration, sharp dose fall off and end of range. In this article, we discuss the Standard Operating Procedure (SOP) for HNC immobilization and simulation for IMPT, developed and practiced at our centre. The SOP details each step during the immobilization and simulation process, with nuances specific to IMPT.

Proton therapy for skull-base adenoid cystic carcinomas: A case series and review of literature.

Purpose: An indolent nature, with a high risk of local recurrence along with the potential for distant metastases, makes the relatively rare adenoid cystic carcinomas (ACCs) of the head-and-neck region, a unique entity. In the base of skull (BOS) region, these cancers require radiation doses as high as 70-72 GyE in proximity to critical structures. Proton therapy (PT) confers physical and radiobiological advantages and local control at 2-5 years exceeding 80% in most series, compared with below 60% with photon-based techniques. We report a case series of ACCs of the BOS, treated with image-guided, intensity-modulated PT (IMPT). Materials and Methods: During 2019-2020, we treated six patients with skull-base ACC IMPT with on-board, cross-sectional image guidance. Dosimetric data, toxicity, and early outcomes were studied, and a comparative review of literature was done. Results: Three patients underwent PT/proton-photon treatment for residual/inoperable lesions and three patients underwent reirradiation for recurrent lesions. The prescription was 70 GyE in 31-35 fractions, and 95% of the clinical target volume (CTV) received 98% of the prescribed dose in five of the six patients. Grade 3 mucositis and skin reactions were noted in two patients and one patient, respectively. Five of the six patients were controlled locally at a median follow-up of 15 months. Conclusion: The radiobiological and physical characteristics of PT help to deliver high doses with excellent CTV coverage in skull-base ACCs, adjacent to critical neurological structures.

Encouraging early outcomes with image guided pencil beam proton therapy for cranio-spinal irradiation: first report from India.

BACKGROUND: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI). MATERIALS AND METHODS: Between January 2019 and December 2021, we carried out a detailed audit of the first forty patients treated with PBT. We had recorded acute toxicities, reporting early outcomes and discuss limitations of current contouring guidelines during CSI PBT planning. RESULTS: Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. Median CSI dose was 23.4 Gy (Gray; range 21.6-35 Gy). Thirty-five patients (87.5%) completed their CSI without interruption, 5 required hospital admission. No patient had grade 2/ > weight loss during the treatment. Forty-five percent (18) developed grade 1 haematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90% patients are alive of whom 88.9% are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients. CONCLUSION: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT.

Challenging case of a re-irradiation in a dorsal spine primitive neuroectodermal tumor: Role of modern image-guided pencil beam proton therapy.

Extradural primary primitive neuroectodermal tumor (PNET) is a rare aggressive disease mostly occurring in young adults. We present a locally recurrent case of dorsal PNET in the fifth decade of life after a prolonged disease-free interval of 10 years. The patient received radiation therapy in fairly large fields twice in his lifetime and was planned for third-time radiation to a few overlapping paraspinal areas over a period of three decades. Keeping in mind previous irradiations, possible target volume in proximity to organs at risk (OARs) patient was planned for consolidtive radiation using the most conformal technique available, which is proton beam therapy with image guided pencil beam scanning technique. Special dose constraints for the spinal cord and other OARs were set, and proton therapy plan was generated at our institute. When compared with parallelly generated intensity-modulated radiation therapy plan with the same dose prescription and dose constraints using helical tomotherapy, intensity-modulated proton therapy plan showed superior dosimetric benefit in terms of coverage and significant sparing of OARs.

Primary diffuse large B cell lymphoma of Uterine Cervix: Treatment outcomes of a rare entity with literature review.

BACKGROUND: Primary lymphomas involving the female genital tract are rare, and those arising from cervix are extremely uncommon. They are often misdiagnosed because of their rarity. METHODS AND CASES: The treatment and clinical outcomes of the four cases treated at our institution were compared with the previously published studies. Written informed consent was taken. We highlight four cases of primary diffuse large B-cell lymphoma of cervix treated at our institution with immunochemotherapy and radiotherapy. The mean age was 50 years (range, 39-62 years). Three patients had stage I disease while one had stage II disease. All the patients were in complete remission following treatment with immunochemotherapy and radiation therapy. The average disease free survival was 20 months (range, 8-43 months). None of the patients had any local or systemic relapse. CONCLUSION: These cases highlight the physicians to be aware of this entity as their management, natural history and prognosis is completely different from squamous carcinomas of the cervix. Surgery should not be attempted in these patients. Immunochemotherapy and radiotherapy results in favorable clinical outcomes.