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.

Proton therapy for reducing heart and cardiac substructure doses in Indian breast cancer patients.

PURPOSE: Indians have a higher incidence of cardiovascular diseases, often at a younger age, than other ethnic groups. This higher baseline risk requires consideration when assessing additional cardiac morbidity of breast cancer treatment. Superior cardiac sparing is a critical dosimetric advantage of proton therapy in breast cancer radiotherapy. We report here the heart and cardiac-substructure doses and early toxicities in breast cancer patients treated post-operatively with proton therapy in India's first proton therapy center. MATERIALS AND METHODS: We treated twenty breast cancer patients with intensity-modulated proton therapy (IMPT) from October 2019 to September 2022, eleven after breast conservation, nine following mastectomy, and appropriate systemic therapy, when indicated. The most prescribed dose was 40 GyE to the whole breast/chest wall and 48 GyE by simultaneous integrated boost to the tumor bed and 37.5 GyE to appropriate nodal volumes, delivered in 15 fractions. RESULTS: Adequate coverage was achieved for clinical target volume (breast/chest wall), i.e., CTV40, and regional nodes, with 99% of the targets receiving 95% of the prescribed dose (V95% > 99%). The mean heart dose was 0.78 GyE and 0.87 GyE for all and left breast cancer patients, respectively. The mean left anterior descending artery (LAD) dose, LAD D0.02cc, and left ventricle dose were 2.76, 6.46, and 0.2 GyE, respectively. Mean ipsilateral lung dose, V20Gy, V5Gy, and contralateral breast dose (Dmean) were 6.87 GyE, 14.6%, 36.4%, and 0.38 GyE, respectively. CONCLUSION: The dose to heart and cardiac substructures is lower with IMPT than published photon therapy data. Despite the limited access to proton therapy at present, given the higher cardiovascular risk and coronary artery disease prevalence in India, the cardiac sparing achieved using this technique merits consideration for wider adoption in breast cancer treatment.

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.

Deep Inspiratory Breath-Hold Radiation for Left-Sided Breast Cancer using Novel Frame-based Tactile Feedback.

A frame providing tactile feedback for the reproducibility of deep inspiratory breath-hold (DIBH) is described. The frame, fitted across the patient, comprises a horizontal bar, parallel to the patient's long axis, and holds a graduated pointer perpendicular to it. The pointer provides individualized tactile feedback for reproducibility of DIBH. Within the pointer is a movable pencil, bearing a 5 mm coloured strip which becomes visible only during DIBH, and acts as a visual cue to the therapist. The average variation in separation in the planning and pretreatment cone-beam computed tomography of 10 patients was 2 mm (confidence interval 1.95-2.05). Frame-based tactile feedback is a novel, reproducible technique for DIBH.

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.

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.

Role of dynamic and parametric whole-body FDG PET/CT imaging in molecular characterization of primary breast cancer: a single institution experience.

AIM: The aim of this pilot study was to assess the role of dynamic whole-body PET and parametric imaging in the biological characterization of primary breast cancer. MATERIALS AND METHOD: In total 24 histologically proven primary breast cancer lesions in 21 consecutive patients were retrospectively analyzed. Each patient underwent 18F-fluoro-deoxyglucose whole-body dynamic PET-CT before any treatment. Dynamic PET images were acquired in the list mode for a total duration of 70 min. The reconstructed parametric imaging generated Patlak plot-based 'Slope' and 'Intercept' images, from which parametric indices ki and DV were obtained. The standard uptake value (SUV) metric was also obtained by summing the last few frames of the dynamic study. ki, distribution volume (DV) and SUV were correlated with the histological tumor grade, biomarkers [hormone receptors and human epidermal growth factor receptor 2 (HER-2) neu expression] and molecular subtypes (A, B and C) as well as with tumor size, regional nodal metastases and distant metastases. RESULTS: The mean ki was found to be significantly higher in grade III than II lesions (P = 0.005), HER-2 neu positive status (P = 0.04) and molecular subtype B (P = 0.04) as well as in greater than T1 lesions(P = 0.0003 and P = 0.04, respectively) and node-positive lesions (P = 0.009). Though mean ki was not found to be significant for the hormone receptors status (P = 0.08), it showed the best correlation compared to the other parameters (P = 0.8 for DV and P = 0.1 for SUV). Spearman's correlation test, area under the curve (AUC) and mismatch percentage also revealed ki to predict tumor grade (AUC, 0.95; r = 0.7; P = 0.0001), HER-2 neu status and molecular subtypes (AUC, 0.81; r = 0.49 and P = 0.01) along with the hormone receptors status (AUC, 0.83; r = 0.32; P = 0.1). The mean DV failed to show any association with any of the biological or anatomical staging parameters. Though ki was found to be comparable to that of SUV in almost all the assessed parameters, it appeared to be better for predicting hormone receptors status even though both parameters were not statistically significant. CONCLUSION: Our initial observation in a small cohort of breast cancer patients suggests that ki is promising in stratifying primary breast cancer lesions according to the tumor grade and biological characteristics.

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.

The Hippocampus: A New Organ at Risk for Postoperative Radiation Therapy for Bucco-alveolar Cancer? A Dosimetric and Biological Analysis.

PURPOSE: A significant proportion of patients with bucco-alveolar cancer are long-term survivors, warranting attention to survivorship issues. Decline in neurocognitive function after cranial irradiation for brain tumors correlates with a hippocampal maximum dose (Dmax) of more than 16 Gy, minimum dose (Dmin) of more than 9 Gy, and dose to 40% of the hippocampal volume (D40%) exceeding 7.3 Gy in 2-Gy equivalent dose (EQD2), respectively. We analyzed the utility of sparing the hippocampus in postoperative radiation therapy (PORT) for patients with bucco-alveolar cancer, given the proximity of target volumes to the hippocampus, by virtue of inclusion of the infratemporal fossa. METHODS AND MATERIALS: We instituted hippocampal sparing for patients with bucco-alveolar cancer receiving PORT in March 2018. Ten prior and 10 subsequent consecutive patients with pathologically staged I-IVA cancers of the buccal mucosa, alveolus, and retromolar trigone formed the control group (no hippocampal sparing) and the study group (hippocampal sparing), respectively. The brain and temporal lobes were prescribed dose constraints in both groups. Patients received doses of 60 to 66 Gy at 2 Gy per fraction using the image-guided intensity modulated radiation therapy / volumetric modulated arc therapy technique. Treatment plans were evaluated for (1) hippocampal dosimetric parameters, (2) planning target volume dosimetry and plan-quality indices, and (3) biological indices of equivalent uniform dose (EUD) and normal-tissue complication probability (NTCP) for impaired neurocognitive function. RESULTS: Hippocampal sparing significantly reduced the hippocampal DmaxEQD2, DmeanEQD2, and D40%EQD2 from 27 Gy to 10.9 Gy (P = .002), 14.3 Gy to 6.4 Gy (P = .002), and 15.5 Gy to 6.6 Gy (P = .005), respectively, with comparable plan-quality indices. The radiobiologically robust endpoints of ipsilateral hippocampal EUD (P = .005) and NTCP (P = .01) were statistically significantly improved. CONCLUSIONS: Meaningful dosimetric benefit, corroborated with radiobiological indices, was observed with hippocampal sparing. The feasibility and benefit of hippocampal sparing supports our view that the hippocampus should be incorporated as an organ at risk and attention should be given to neurocognitive function in patients with bucco-alveolar cancer who are receiving PORT.

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India.

PURPOSE: Proton beam therapy (PBT) has been a preferred modality in pediatric malignancies requiring radiotherapy. We report our preliminary experience of treating consecutive patients younger than 25 years with image-guided pencil beam scanning PBT from the first and only center on the Indian subcontinent. METHODS: Patients were selected for PBT on the basis of a multidisciplinary tumor board decision. Patient demographic data, as well as tumor and treatment-related characteristics of the cohort, were captured. Patient and treatment-related factors and their association with acute toxicities were analyzed using univariable and multivariable analyses. RESULTS: Forty-seven patients (27 with CNS and 20 with non-CNS tumors) with a median age of 9 years (range, 2-25 years) were evaluated. Most common diagnoses were ependymoma, rhabdomyosarcoma, and glioma. Seventy-seven percent of patients traveled more than 500 km, and 70% of them lived in metropolitan cities. Forty-nine percent of patients had recurrent disease at presentation, and 15% had received a previous course of radiation. The median dose delivered was 54.8 cobalt gray equivalents (range, 40.0-70.4 cobalt gray equivalents) to a median clinical target volume of 175 mL (range, 18.7-3,083.0 mL), with 34% of patients requiring concurrent chemotherapy (CCT). Acute grade 2 and grade 3 dermatitis, mucositis, and hematologic toxicity was noted in 45% and 2%, 34% and 0%, and 38% and 30% of patients, respectively. Grade 2 fatigue was noted in 26% of patients. On multivariable analysis, for CNS tumors, both CCT and craniospinal irradiation were independently associated with ≥ 2 grade hematologic toxicity, whereas among non-CNS tumors, a clinical target volume > 150 mL was associated with ≥ 2 grade fatigue, head and neck irradiation was associated with ≥ 2 grade mucositis, and CCT was associated with grade ≥ 2 hematologic toxicity. CONCLUSION: This study demonstrates safe implementation of a PBT program for children and young adults on the Indian subcontinent. Image-guided pencil beam scanning PBT in judiciously selected patients is feasible and can be delivered with acceptable acute toxicities.

Adjuvant conundrum in central mucoepidermoid carcinoma of the mandible: case presentation and literature review.

The cornerstone modality of treatment of central mucoepidermoid carcinoma (CMEC) of the mandible is surgery, optimally, an en bloc resection with/without segmental or hemimandibulectomy. Notwithstanding the documentation of a survival benefit in few case reports with the addition of postoperative radiotherapy in carefully selected high-risk patients, there does not exist a clearly defined consensus regarding the role of adjuvant radiotherapy. We report the case of a 49-year-old man who presented with right lower jaw swelling which on imaging was found to be a multiloculated lesion causing bony expansion and cortical destruction of the mandible and was diagnosed with CMEC after radiological and histopathological criteria were met. He underwent right hemimandibulectomy and histopathology showed squamous and mucinous cells with positive mucicarmine staining and characteristic immunohistochemistry markers confirming the diagnosis of CMEC. He subsequently underwent adjuvant radiotherapy and is disease free 5 years since treatment completion.

Metachronous solitary plasmacytoma.

Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell neoplasms. Progression to multiple myeloma is the most common pattern of relapse. Appearance of new lesions without any systemic disease is the most unusual pattern of relapse seen in <2% cases. We present a case of a 46-year-old female who presented with features of third and seventh cranial nerve palsy, diagnosed with solitary plasmacytoma, with no evidence of any systemic disease. As per standard recommendations, the patient received radiotherapy to the local site. The patient developed relapse twice, at three sites, during the follow-up period. Investigations revealed no evidence of any systemic disease. In view of repeat relapses, the patient was started on immune modulatory agent. Two and half years after the last radiotherapy, the patient is symptom free with no evidence of any new lesion.

A technique to reduce low dose region for craniospinal irradiation (CSI) with RapidArc and its dosimetric comparison with 3D conformal technique (3DCRT).

We proposed a method to reduce the volume of normal tissues irradiated by low doses in patients receiving CSI with RapidArc (RA) using Avoidance-Sector technique (RA+AS) and to compare its dosimetric implications with RA using full-arc (RA+FA) and 3D conformal technique (3DCRT). Four patients of CSI were retrospectively planned with 3DCRT, RA+FA, and RA+AS. Conformity-Index (CI), Homogeneity-Index (HI), and Paddick Gradient-Index (GI) were calculated. Quantitative evaluation was done using DVH analysis for PTVs and OARs. When compared with 3DCRT, GI, CI, and HI were favorable to RA based techniques. In comparison with 3DCRT the doses to OARs were lower with RA+AS with the difference being statistically significant in most instances. RA+AS significantly decreases the dose to OARs and their volumes receiving low doses in comparison with RA+FA and 3DCRT.

Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient.

INTRODUCTION: While planning radiation therapy (RT) for a carcinoma of the urinary bladder (CaUB), the intra-fractional variation of the urinary bladder (UB) volume due to filling-up needs to be accounted for. This internal target volume (ITV) is obtained by adding internal margins (IM) to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. METHODS: One patient with CaUB underwent simulation with the proposed 'bladder protocol'. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T) was noted. Planning CT scans were performed after 20 min (T+20), 30 min (T+30) and 40 min (T+40). The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT) scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30. RESULTS: In total, there were 65 CBCT scans (36 pre- and 29 post-treatment). Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances. CONCLUSIONS: The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.

Daily online localization using implanted fiducial markers and its impact on planning target volume for carcinoma prostate.

BACKGROUND: Aim of the study was to assess prostate motion on daily basis with respect to setup and to compare the shifts based on bony anatomy and gold fiducial markers. MATERIALS AND METHODS: Gold fiducial markers were inserted in prostate under U/S guidance and daily portal images were taken and compared with digitally reconstructed images, both using bony landmarks and fiducial markers as reference. A dose of 2 MU was given for two orthogonal images daily. The mean and standard deviation of displacement using gold seeds and bone were calculated. Systematic and random errors were generated. The planning target volume (PTV) was calculated using the Van Herk formula. RESULTS: A total of 180 portal images from 10 patients were studied. The mean displacement along x, y and z axes was 1.67 mm, 3.58 mm, and 1.76 mm using fiducial markers and 2.12 mm, 3.47 mm, and 2.09 mm using bony landmarks, respectively. The mean internal organ motion was 1.23 mm (+1.45), 3.11 mm (+2.69 mm); and 1.87 mm (+1.67 mm) along x, y and z axes, respectively. The PTV to account for prostate motion if daily matching was not done was 4.64 mm, 10.41 mm and 4.40 mm along lateral, superoinferior, and anteroposterior directions, respectively. If bony landmarks were used for daily matching, margins of 3.61 mm, 7.31 mm, and 4.72 mm in lateral, superoinferior, and anteroposterior directions should be added to the clinical target volume. CONCLUSION: Daily alignment using gold fiducial markers is an effective method of localizing prostate displacement. It provides the option of reducing margins, thus limiting normal tissue toxicity and allowing the possibility of dose escalation for better long-term control.

Selective nodal irradiation for head and neck cancer using intensity-modulated radiotherapy: application of RTOG consensus guidelines in routine clinical practice.

PURPOSE: We have been using intensity-modulated radiotherapy (IMRT) for selective neck irradiation. This article presents an analysis of patterns of failure and their dosimetric correlation. METHODS AND MATERIALS: Between October 2003 and January 2008, 83 patients with head-and-neck cancer were treated with IMRT. Nodal levels were contoured as per the Radiation Therapy Oncology Group (RTOG) consensus guidelines. RESULTS: There were 32 relapses with 23 local relapses (21 local relapses alone and 2 local and regional relapses, simultaneously), 9 regional relapses (including 2 simultaneous local and regional relapses), and 5 distant relapses, of which 2 patients had local relapses. At 2 and 3 years, the locoregional relapse-free survival rates were was 68.3% and 60.8%, respectively, while the overall survival rates were 84.1% and 81.7%, respectively. Subgroup analyses revealed significant differences in locoregional relapse-free survival rates for total treatment times of <53 days vs. >53 days, a volume of CTV1PTV (i.e., the volume prescribed 70 Gy) <177 cc vs. >177 cc, a V100 for CTV1PTV of <91% vs. >91%, and a minimum dose to CTV1PTV of <54 Gy vs. >54 Gy. There were no failures in the elective nodal volume, substantiating both the nodal selection criteria and the RTOG consensus guidelines for delineation of neck node levels. CONCLUSIONS: IMRT for head-neck cancer is feasible, using elective nodal selection criteria along with RTOG consensus guidelines for the radiological boundaries of levels of neck nodes.