Evaluation of Tumor Control and Normal Tissue Complication Probabilities in Patients Receiving Comprehensive Nodal Irradiation for Left-Sided Breast Cancer.

Women with left-sided breast cancer receiving adjuvant radiotherapy have increased incidence of cardiac mortality due to ischemic heart disease; to date, no threshold dose for late cardiac/pulmonary morbidity or mortality has been established. We investigated the likelihood of cardiac death and radiation pneumonitis in women with left-sided breast cancer who received comprehensive lymph node irradiation. The differences in dosimetric parameters between free-breathing (FB) and deep inspiration breath hold (DIBH) techniques were also addressed. Based on NTCP calculations, the probability of cardiac death was significantly reduced with the DIBH compared to the FB technique (p < 0.001). The risk of radiation pneumonitis was not clinically significant. There was no difference in coverage between FB and DIBH plans. Doses to healthy structures were significantly lower in DIBH plan than in FB plan for V20, V30, and ipsilateral total lung volume. Inspiratory gating reduces the dose absorbed by the heart without compromising the target range, thus reducing the likelihood of cardiac death.

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.

Pelvic bone marrow dose-volume predictors of late lymphopenia following pelvic lymph node radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study. MATERIALS AND METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/µL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap. RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation. CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.

Assessment of lymph node area coverage with total marrow irradiation and implementation of total marrow and lymphoid irradiation using automated deep learning-based segmentation.

BACKGROUND: Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have the advantages. However, delineating target lesions according to TMI and TMLI plans is labor-intensive and time-consuming. In addition, although the delineation of target lesions between TMI and TMLI differs, the clinical distinction is not clear, and the lymph node (LN) area coverage during TMI remains uncertain. Accordingly, this study calculates the LN area coverage according to the TMI plan. Further, a deep learning-based model for delineating LN areas is trained and evaluated. METHODS: Whole-body regional LN areas were manually contoured in patients treated according to a TMI plan. The dose coverage of the delineated LN areas in the TMI plan was estimated. To train the deep learning model for automatic segmentation, additional whole-body computed tomography data were obtained from other patients. The patients and data were divided into training/validation and test groups and models were developed using the "nnU-NET" framework. The trained models were evaluated using Dice similarity coefficient (DSC), precision, recall, and Hausdorff distance 95 (HD95). The time required to contour and trim predicted results manually using the deep learning model was measured and compared. RESULTS: The dose coverage for LN areas by TMI plan had V100% (the percentage of volume receiving 100% of the prescribed dose), V95%, and V90% median values of 46.0%, 62.1%, and 73.5%, respectively. The lowest V100% values were identified in the inguinal (14.7%), external iliac (21.8%), and para-aortic (42.8%) LNs. The median values of DSC, precision, recall, and HD95 of the trained model were 0.79, 0.83, 0.76, and 2.63, respectively. The time for manual contouring and simply modified predicted contouring were statistically significantly different. CONCLUSIONS: The dose coverage in the inguinal, external iliac, and para-aortic LN areas was suboptimal when treatment is administered according to the TMI plan. This research demonstrates that the automatic delineation of LN areas using deep learning can facilitate the implementation of TMLI.

Internal Mammary Node Irradiation Debate: Case Closed? Not Yet, and Maybe Never.

The IMN debate is still open and may never be closed for reasons outlined in this Comments and Controversies piece.

Modern Radiation for Hematologic Stem Cell Transplantation: Total Marrow and Lymphoid Irradiation or Intensity-Modulated Radiation Therapy Total Body Irradiation.

The development of large-field intensity-modulated radiation therapy (IMRT) has enabled the implementation of total marrow irradiation (TMI), total marrow and lymphoid irradiation (TMLI), and IMRT total body irradiation (TBI). IMRT TBI limits doses to organs at risk, primarily the lungs and in some cases the kidneys and lenses, which may mitigate complications. TMI/TMLI allows for dose escalation above TBI radiation therapy doses to malignant sites while still sparing organs at risk. Although still sparingly used, these techniques have established feasibility and demonstrated promise in reducing the adverse effects of TBI while maintaining and potentially improving survival outcomes.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

External radiotherapy for prostatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.

Mathematical evaluation of post-radiotherapy salivary gland function using salivary gland scintigraphy.

OBJECTIVE: Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function. METHODS: Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later. RESULTS: The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group (n = 10), 56% in the conformal radiotherapy group (n = 15), and 44% in the bioradiotherapy group (n = 6). CONCLUSION: Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT. ADVANCES IN KNOWLEDGE: In this study, the average tolerated dose to the salivary glands was 46 Gy.

Radiotherapy of salivary gland tumours.

Primary tumours of the salivary glands account for about 5 to 10% of tumours of the head and neck. These tumours represent a multitude of situations and histologies, where surgery is the mainstay of treatment and radiotherapy is frequently needed for malignant tumours (in case of stage T3-T4, nodal involvement, extraparotid invasion, positive or close resection margins, histological high-grade tumour, lymphovascular or perineural invasion, bone involvement postoperatively, or unresectable tumours). The diagnosis relies on anatomic and functional MRI and ultrasound-guided fine-needle aspiration for the diagnostic of benign or malignant tumors. In addition to patient characteristics, the determination of primary and nodal target volumes depends on tumor extensions and stage, histology and grade. Therefore, radiotherapy of salivary gland tumors requires a certain degree of personalization, which has been codified in the recommendations of the French multidisciplinary network of expertise for rare ENT cancers (Refcor) and may justify a specialised multidisciplinary discussion. Although radiotherapy is usually recommended for malignant tumours only, recurrent pleomorphic adenomas may sometimes require radiotherapy based on multidisciplinary discussion. An update of indications and recommendations for radiotherapy for salivary gland tumours in terms of techniques, doses, target volumes and dose constraints to organs at risk of the French society for radiotherapy and oncology (SFRO) was reported in this article.

Radiotherapy for penile cancers.

Penile cancers are uncommon and should be treated in expert center. Radiotherapy indications are mainly limited to exclusive brachytherapy for early stage penile glans cancer. Brachytherapy yields to excellent outcome for disease control and organ and function preservation. Only scarce data are available for external beam radiation therapy. It could be considered as palliative setting for irradiation of the primary tumor. For lymph node irradiation, external beam radiation therapy (with or without chemotherapy) could be discussed either as neoadjuvant approach prior to surgery for massive inguinal lymph node invasion or as adjuvant approach in case of high-risk of relapse. However, these cases should be discussed on an individual basis, as the level of evidence is poor. We present the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for penile glans cancer.

Cardiopulmonary-related patient-reported outcomes in a randomized clinical trial of radiation therapy for breast cancer.

BACKGROUND: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity. METHODS: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain. RESULTS: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029. CONCLUSION: Modern radiation therapy can significantly improve long-term PRO. TRIAL REGISTRATION: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively.

De-escalation of axillary irradiation for early breast cancer - Has the time come?

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

Role of radiotherapy for high risk localized prostate cancers.

Management of high-risk prostate cancers is still a subject of debate, because of the lack of randomized trial comparing surgery and radiotherapy. If external beam radiotherapy is proposed, it must be associated with a long-term androgen deprivation therapy, at least 18-months. Irradiation of pelvic lymph nodes seems to improve distant metastasis-free survival and is so indicated in most of the cases. Moderate hypofractionation is not validated for pelvic lymph nodes irradiation. A combination of external beam radiotherapy and brachytherapy improved biochemical control in randomized trials without impact on survival. But this combination has been evaluated in large retrospective studies and seems to improve specific and overall survivals. An integrated boost on the MRI-defined index lesion is another way of dose escalation and improved also biochemical control. Stereotactic radiotherapy is not a validated option at this moment. For each patient, according to the extension of the disease, age, comorbidities and also his willingness, the best approach must be chosen, ideally in multidisciplinary meeting.

High dose simultaneous integrated boost for node positive cervical cancer.

INTRODUCTION: Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes. MATERIALS AND METHODS: Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS). RESULTS: In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity. CONCLUSION: Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation.

[Diffusion prophylactic axillary irradiation in breast cancer - Literature review]. / Irradiation axillaire prophylactique « de diffusion ¼ dans le cancer du sein ­ revue de la littérature.

PURPOSE: In breast cancer, radiotherapy is an essential component of the treatment. However, indications of irradiation of the internal mammary chain and axillary area are debatables. Axillary recurrence in patients with invasive breast carcinoma remains an issue. Currently, the substitution of axillary lymph node dissection by sentinel node biopsy leads to revisit the role of axillary irradiation. Breast irradiation including level I, II and III might decrease the risk of axillary recurrence. MATERIAL AND METHODS: A literature search was performed in PubMed and the Cochrane library to identify articles publishing data regarding dose-volume analysis of axillary levels in breast irradiation aiming to determine the potential therapeutic implications. RESULTS: Eleven articles were retained. A total of 375 treatment plans were analyzed. The results concerning the irradiation technique, initial dose prescribed to breast, delineated volumes and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I-III with 3D-conformal radiotherapy using standard fields were between 24Gy and 43.5Gy, 3Gy and 32.5Gy and between 1.0Gy and 20.5Gy respectively. The average doses delivered to axilla levels I-III with 3D-conformal radiotherapy using high tangential fields were between 38Gy and 49.7Gy, 11Gy and 47.1Gy and 5Gy 38.7Gy, 32.1Gy and 5Gy (result available for only one study) respectively. Finally, the average doses delivered to axilla levels I-III with intensity modulated radiation therapy were between 14.5Gy and 42.6Gy, 3.4Gy and 35Gy and between 1.2Gy and 25.5Gy respectively. CONCLUSIONS: Incidental axillary dose seems insufficient to be therapeutic regardless of the irradiation technique. There are meaningful differences between intensity modulated radiation therapy and 3D-conformal radiotherapy.

Evaluation of margins in pelvic lymph nodes and prostate radiotherapy and the impact of bladder and rectum on prostate position.

PURPOSE: The aims of this study were: determination of the CTV to PTV margins for prostate and pelvic lymph nodes. Investigation of the impact of registration modality (pelvic bones or prostate) on the CTV to PTV margins of pelvic lymph nodes. Investigation of the variations of bladder and rectum over the treatment course. Investigation of the impact of bladder and rectum variations on prostate position. PATIENTS AND METHODS: This study included 15 patients treated for prostate adenocarcinoma. Daily kilo voltage images and weekly CBCT scans were performed to assess prostate displacements and common and external iliac vessels motion. These data was used to calculate the CTV to PTV margins using Van Herk equation in the setting of a daily bone registration. We also compared the CTV to PTV margins of pelvic lymph nodes according to registration method; based on pelvic bone or prostate. We delineated bladder and rectum on all CBCT scans to assess their variations over treatment course at 4 anatomic levels [1.5cm above pubic bone (PB), superior edge, mid- and inferior edge of PB]. RESULTS: Using Van Herk equation, the prostate CTV to PTV margins (bone registration) were 8.03mm, 5.42mm and 8.73mm in AP, ML and SI direction with more than 97% of prostate displacements were less than 5mm. The CTV to PTV margins ranged from 3.12mm to 3.25mm for external iliac vessels and from 3.12mm to 4.18mm for common iliac vessels. Compared to registration based on prostate alignment, bone registration resulted in an important reduction of the CTV to PTV margins up to 54.3% for external iliac vessels and up to 39.6% for common iliac vessels. There was no significant variation of the mean bladder volume over the treatment course. There was a significant variation of the mean rectal volume before and after the third week of treatment. After the third week, the mean rectal volume seemed to be stable. The uni- and multivariate analysis identified the anterior wall of rectum as independent factor acting on prostate motion in AP direction at 2 levels (superior edge of, mid PB). The right rectal wall influenced the prostate motion in ML direction at inferior edge of PB. The bladder volume tends toward significance as factor acting on prostate motion in AP direction. CONCLUSIONS: We recommend CTV to PTV margins of 8mm, 6mm and 9mm in AP, ML and SI directions for prostate. And, we suggest 4mm and 5mm for external and common iliac vessels respectively. We also prefer registration based on bony landmarks to minimize bowel irradiation. More CBCT scans should be performed during the first 3weeks and especially the first week to check rectum volume.

Clinical Effectiveness of an Adaptive Treatment Planning Algorithm for Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Node-Positive Breast Cancer Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy.

PURPOSE: Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. METHODS AND MATERIALS: Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). RESULTS: Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). CONCLUSIONS: An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

Toxicity of Pelvic Lymph Node Irradiation With Intensity Modulated Radiation Therapy for High-Risk and Locally Advanced Prostate Cancer: A National Population-Based Study Using Patient-Reported Outcomes.

PURPOSE: Little is known about the toxicity of additional pelvic lymph node irradiation in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. The aim of this study was to compare patient-reported outcomes after IMRT to the prostate only (PO-IMRT) versus the prostate and pelvic lymph nodes (PPLN-IMRT). METHODS AND MATERIALS: Patients who received a diagnosis of high-risk or locally advanced prostate cancer in the English National Health Service between April 2014 and September 2016 who were treated with IMRT were mailed a questionnaire at least 18 months after diagnosis. Patient-reported urinary, sexual, bowel, and hormonal functional domains on a scale from 0 to 100, with higher scores indicating better outcomes, and generic health-related quality of life were collected using the Expanded Prostate Cancer Index Composite 26-item version and EQ-5D-5L. We used linear regression to compare PPLN-IMRT versus PO-IMRT with adjustment for patient, tumor, and treatment characteristics. RESULTS: Of the 7017 men who received a questionnaire, 5468 (77.9%) responded; 4196 (76.7%) had received PO-IMRT and 1272 (23.3%) PPLN-IMRT. Adjusted differences in the Expanded Prostate Cancer Index Composite 26-item version domain scores were smaller than 1 (P always >.2), except for sexual function, with men who had PPNL-IMRT reporting a lower mean score (adjusted difference, 2.3; 95% confidence interval, 0.9-3.7; P = .002). This did not represent a clinically relevant difference. There was no significant difference in health-related quality of life (P = .5). CONCLUSIONS: Additional pelvic lymph node irradiation does not lead to clinically meaningful increases in the toxicity of IMRT for prostate cancer according to patient-reported functional outcomes and health-related quality of life.

Axillary nodal irradiation practice in the sentinel lymph node biopsy era: Comparison of the contemporary available 3D and IMRT techniques.

OBJECTIVE: Our study aimed to compare regional node coverage and doses to the organ at risk (OAR) using conventional technique (CT) vs "AMAROS" (AT) vs intensity-modulated radiation therapy (IMRT) techniques in patients receiving regional nodal irradiation (RNI) for breast cancer (BC). METHODS: We included 30 consecutive patients with BC who received RNI including axillary nodes. Two independent and blinded dosimetric RNI plans were generated for all patients. For target volume coverage, we analyzed the V95%, the D95%, the mean and the minimal dose within the nodal station. For hotspots within nodal target volume, we used the V105%, the V108% and the maximal doses. For OAR, lung V20, mean lung and heart doses, the maximal dose to the brachial plexus and the axillary-lateral thoracic vessel junction region were compared between the three techniques. RESULTS: Target volume coverage and hotspots: Mean V95% in stations I, II, III and IV were 35.8% and 75% respectively with CV, 22.59 and 59.9% respectively with AT technique and 45.58 and 99.6% respectively with IMRT with statistically significant differences (p < 0.001). Mean V105% (cc) in axillary and supraclavicular stations were 21.3 and 6.4 respectively with CV, 1.2 and 0.02 respectively with AT technique and 0.5 and 0.4 respectively with IMRT with statistically significant differences (p < 0.001)..OARs: The mean ipsilateral lung V20 was 16.9%, 16.4 and 13.3% with CT, AT and IMRT respectively. The mean heart dose (Gy) was 0.3, 0.2 and 0.2 with CT, AT and IMRT respectively. The maximal dose to the plexus brachial (Gy) was 50.3, 46.3 and 47.3 with CT, AT and IMRT respectively. The maximal dose to the axillary-lateral thoracic vessel junction (Gy) was 52.3, 47.3 and 47.6 with CT, AT and IMRT respectively. The differences were statistically significant for all OAR (p < 0.001). CONCLUSION: AT is a valuable technique for RNI including axilla in patients with limited sentinel lymph node biopsy involvement without additional axillary lymph node dissection since it decreases hotspots in the target volume and lowers the radiation exposure of the OAR. For more advanced tumors or patients who did not respond to primary systemic therapy, CT or IMRT should be considered because of their better coverage of the potentially residual nodal disease. IMRT combines several advantages of offering high conformal plans, limited hotspots and protection of main OAR. The clinical impact of these dosimetric differences need to be addressed. ADVANCES IN KNOWLEDGE: This study is to our knowledge the first to compare conventional three-dimensional and IMRT techniques for regional nodal irradiation for each nodal station in breast cancer in a context of increasing utilization of axillary irradiation.