The effect of incidental dose to pelvic nodes in bladder-only irradiation in the era of IMRT: a dosimetric study.

PURPOSE: While three-dimensional radiotherapy (RT) causes high incidental nodal doses in bladder-only irradiation for muscle-invasive bladder cancer (MIBC), the impact on pelvic lymphatics is unclear in the era of intensity-modulated RT (IMRT). This study evaluates incidental doses to pelvic lymphatics in MIBC patients treated with IMRT. METHODS: The data of 40 MIBC patients treated with bladder-only IMRT and concurrent chemotherapy were retrospectively evaluated. The pelvic lymphatics were contoured on initial simulation images and incidental nodal doses were evaluated. The Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Median RT dose to the bladder was 60 Gy in 30 fractions. In dosimetric analysis, median values of mean dose (Dmean) of the obturator, presacral, external iliac, internal iliac, and distal common iliac lymphatics were 33 Gy (range 4-50 Gy), 3 Gy (range 1-28 Gy), 9.5 Gy (range 3-41 Gy), 7.5 Gy (range 2-14 Gy), and 1 Gy (range 0-15 Gy), respectively. The Dmean of the obturator lymphatics was significantly higher (p < 0.001) and the Dmean of the distal common iliac lymphatics was significantly lower (p < 0.001) than all remaining lymphatic stations. The Dmean of the external iliac lymphatics was significantly higher than that of the presacral lymphatics (p < 0.001), but the difference with the internal iliac lymphatics was not statistically significant (p = 0.563). CONCLUSION: The incidental nodal doses with bladder-only IMRT are heterogeneous and remain below the generally accepted doses for microscopic disease eradication for bladder cancer.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .

Axillary Management: How Much Is Too Much?

PURPOSE OF REVIEW: To review the current management of the axilla in breast cancer. RECENT FINDINGS: Axillary dissection is no longer indicated in patients with clinically node-negative axilla with 1-2 positive sentinel lymph nodes following upfront surgery or in patients with clinically node-negative axilla following neoadjuvant chemotherapy. Breast cancer has evolved away from routine axillary clearance to the less invasive sentinel lymph node biopsy to now complete omission of axillary sampling in select patients. We will review the most salient evidence that has shaped these practice changes over the last three decades. Current practice controversies are especially relevant for elderly populations and those receiving neoadjuvant therapy. Ongoing clinical trials will provide data to further guide breast cancer surgical management.

A phase III randomized controlled trial comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer: ARMADILLO trial (JCOG1904).

Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).

HYpofractionated, dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase I HYDRA trial.

BACKGROUND: Radiotherapy (RT) is the standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%. Despite strong biological rationale, combining RT with immune checkpoint inhibitors does not result in a survival benefit. Our hypothesis is that the combination of these individually effective treatments fails because of radiation-induced immunosuppression and lymphodepletion. By integrating modern radiobiology and innovative radiotherapy concepts, the patient's immune system could be maximally retained by (1) increasing the dose per fraction so that the total dose and number of fractions can be reduced (HYpofractionation), (2) redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective lymphatic field dose (Dose-redistribution), and (3) using RAdiotherapy with protons instead of photons (HYDRA). METHODS: The primary aim of this multicenter study is to determine the safety of HYDRA proton- and photon radiotherapy by conducting two parallel phase I trials. Both HYDRA arms are randomized with the standard of care for longitudinal immune profiling. There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated immunoradiotherapy trials. The HYDRA dose prescriptions (in 20 fractions) are 40 Gy elective dose and 55 Gy simultaneous integrated boost on the clinical target volume with a 59 Gy focal boost on the tumor center. A total of 100 patients (25 per treatment group) will be recruited, and the final analysis will be performed one year after the last patient has been included. DISCUSSION: In the context of HNSCC, hypofractionation has historically only been reserved for small tumors out of fear for late normal tissue toxicity. To date, hypofractionated radiotherapy may also be safe for larger tumors, as both the radiation dose and volume can be reduced by the combination of advanced imaging for better target definition, novel accelerated repopulation models and high-precision radiation treatment planning and dose delivery. HYDRA's expected immune-sparing effect may lead to improved outcomes by allowing for future effective combination treatment with immunotherapy. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov; NCT05364411 (registered on May 6th, 2022).

A Precise Approach for Radiotherapy of Breast Cancer.

Radiotherapy is an integral part of the multidisciplinary management of breast cancer (BC). There have been multiple recent advances in the delivery of radiotherapy, reviewed with a critical discussion of the evidence from trials investigating adjuvant ultra-hypofractionation and partial breast irradiation for early-stage BC, and the locoregional management of lymph nodes in locally advanced BC. Multiple precision medicine-based approaches have been developed as prognostic and/or predictive for BC patients and identifying biomarkers of radioresistance could help identify patients that may benefit from dose-escalated radiotherapy or radiosensitizers. Radiotherapy after breast reconstruction is an area of current controversy in the field, and we evaluated the decision-making considerations in this situation. The oligometastatic state is an emerging field for many cancer sites based on recent trials investigating ablative radiotherapy for oligometastatic BC. This chapter is an overview of radiotherapy for BC, with a focus on recent advances in early-stage, locally advanced, and oligometastatic disease.

A comparison of acute patient-reported outcomes in breast cancer patients with and without regional nodal irradiation using the ESAS and PRFS tool.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) is commonly administered in patients with breast cancer with node-positive disease to prevent cancer recurrence. The purpose of this study is to identify whether RNI is associated with greater acute symptom burden from baseline to 1 to 3 months post completion of radiotherapy (RT) when compared to localized RT. MATERIALS AND METHODS: Patient and treatment characteristics were collected prospectively for breast cancer patients with and without RNI from February 2018 to September 2020. The Edmonton Symptom Assessment System (ESAS) and Patient-Reported Functional Status (PRFS) tool were completed by patients at baseline, weekly during RT, and at a 1- to 3-month follow-up visit. The Wilcoxon rank-sum or Fisher exact tests were used to compare variables between patients with or without RNI. RESULTS: A total of 781 patients were included in the analysis. Baseline symptom reporting was similar between cohorts, with the exception of PRFS scores (p = 0.0023), which were worse in patients receiving RNI. Across all time points, differences in outcomes between cohorts were minimal, except for lack of appetite (p = 0.03) and PRFS scores (p = 0.049), which were significantly aggravated in patients treated with RNI. CONCLUSION: There is insufficient evidence to suggest that RNI is associated with greater symptom burden as assessed with the ESAS. Further research should be conducted over a longer time period to determine the impact of late effects of RNI on patient-reported symptoms.

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

BACKGROUND: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. RESULTS: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. CONCLUSION: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Caution against simultaneous integrated boost radiotherapy for upper thoracic esophageal squamous cell carcinoma: results from a single-arm phase II trial.

PURPOSE: To explore the feasibility and safety of simultaneous integrated boost technology (SIB) with elective nodal irradiation (ENI) to the cervical and upper mediastinal lymph node (LN) regions in upper thoracic esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS: Patients with pathologically proven unresectable upper thoracic ESCC were assigned 50.4 Gy/28 fractions (F) to the clinical target volume (encompassing the ENI area of cervical and upper mediastinal LN regions) and a boost of 63 Gy/28 F to the gross tumor volume. Chemotherapy consisted of courses of concurrent cisplatin (20 mg/m2) and docetaxel (20 mg/m2) weekly for 6 weeks. The primary endpoint was toxicity. RESULTS: Between Jan 2017 and Dec 2019, 28 patients were included. The median follow-up time for all patients was 24.6 months (range 1.9-53.5). Radiation-related acute toxicity included esophagitis, pneumonia and radiodermatitis, all of which were well managed and reversed. Late morbidity included esophageal ulcer, stenosis, fistula and pulmonary fibrosis. Grade III esophageal stenosis and fistula was seen in 11% (3/28) and 14% (4/28) patients, respectively. The cumulative incidence rate of late esophageal toxicity was 7.7%, 19.2% and 24.6% at 6, 12 and 18 months, respectively. There was significant difference of the occurrence of severe late esophageal toxicity among the different volume levels of the esophagus, and cervical and upper mediastinal LNs which received ≥ 63 Gy stratified by the tertiles (p = 0.014). CONCLUSIONS: Despite the acceptably tolerated acute toxicity of SIB in concurrent CRT with ENI to the cervical and upper mediastinal LN regions for upper thoracic ESCC, the incidence of severe late esophageal toxicity was relatively high. Cautions are provided against easy clinical application of SIB (50.4 Gy/28F to the CTV, 63 Gy/28F to the GTV) in upper thoracic ESCC. Further exploration on dose optimization is warranted.

Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation.

PURPOSE: This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. MATERIALS AND METHODS: Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. RESULTS: Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8-138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5-138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported. CONCLUSION: In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

A comparative study evaluating the dose volume parameters in 3D conformal radiation of left sided whole breast irradiation including regional lymphnodes - a need of resource constrained countries.

BACKGROUND: The purpose of this study was to compare four 3D conformal radiation techniques in treatment of left breast cancer patients. MATERIALS AND METHODS: Radiation was planned for 20 patients to the left breast and regional lymph nodes using four techniques: partially wide tangents, photon-photon mix, photon-electron mix and 30/70 photon-electron mix. All plans were evaluated for internal mammary nodes (IMN) coverage, hotspot and normal tissue constraints. RESULT: The 85% of planning target volume (PTV) coverage was lesser for upper IMN than the lower IMN (below the lower border of the clavicular head) for all four techniques. The lower IMN coverage was better for partially wide tangent (80.46%) and photon-photon mix (88.88%). The lowest value of hotspot was seen in the partially wide tangent technique (112.69% ± 1.92). Hotspot is unacceptably high in both photon-electron mix and 30/70 photon-electron mix (> 120%). Left lung mean dose for all techniques on a pair-wise comparison showed no statistical difference. Left lung V20 values for partially wide tangent was 37.56% ± 8.17 and for photon-photon mix it was 40.49% ± 3.36. The mean heart dose with partially wide tangent was 9.43 ± 3.15 Gy and with photon-photon mix it was 10.10 ± 2.70 Gy. The mean heart dose for photon-electron mix was 7.56 ± 1.95 Gy and for 30/70 photon-electron mix it was 7.98 ± 2.16 Gy. CONCLUSION: No single technique satisfies all the criteria. The decision should be made on a case-by-case basis, considering the anatomy of the patient, availability of electron facilities and setup accuracy and reproducibility.

A historical literature review on the role of posterior axillary boost field in the axillary lymph node coverage and development of lymphedema following regional nodal irradiation in breast cancer.

To elucidate whether (1) a posterior axillary boost (PAB) field is an optimal method to target axillary lymph nodes (LNs); and (2) the addition of a PAB increases the incidence of lymphedema, a systematic review was undertaken. A literature search was performed in the PubMed database. A total of 16 studies were evaluated. There were no randomized studies. Seven articles have investigated dosimetric aspects of a PAB. The remaining 9 articles have determined the effect of a PAB field on the risk of lymphedema. Only 2 of 9 articles have prospectively reported the impact of a PAB on the risk of lymphedema development. There are conflicting reports on the necessity of a PAB. The PAB field provides a good coverage of level I/II axillary LNs because these nodes are usually at a greater depth. The main concern regarding a PAB is that it produces a hot spot in the anterior region of the axilla. Planning studies optimized a traditional PAB field. Prospective studies and the vast majority of retrospective studies have reported the use of a PAB field does not result in increasing the risk of lymphedema development over supraclavicular-only field. The controversies in the incidence of lymphedema suggest that field design may be more important than field arrangement. A key factor regarding the use of a PAB is the depth of axillary LNs. The PAB field should not be used unless there is an absolute indication for its application. Clinicians should weigh lymphedema risk in individual patients against the limited benefit of a PAB, in particular after axillary dissection. The testing of the inclusion of upper arm lymphatics in the regional LN irradiation target volume, and universal methodology measuring lymphedema are all areas for possible future studies.

Axillary management for young women with breast cancer varies between patients electing breast-conservation therapy or mastectomy.

PURPOSE: Axillary treatment strategies for the young woman with early-stage, clinically node-negative breast cancer undergoing upfront surgery found to have 1-3 positive sentinel lymph nodes (SLNs) differ significantly after BCT and mastectomy. Here we compare axillary lymph node dissection (ALND) and regional nodal irradiation (NRI) rates between women electing breast-conservation therapy (BCT) versus mastectomy. METHODS: From 2010 to 2016, women age < 50 years with clinical T1-T2N0 breast cancer having upfront surgery and found to have a positive SLN were identified. ALND and/or NRI receipt were compared between groups. RESULTS: 192 women undergoing BCT and 165 undergoing mastectomy were identified (median age: 44 years). 5.2% (10/192) of women undergoing BCT had an ALND versus 87% (144/165) of women undergoing mastectomy (p < 0.01). NRI was given to 48% (78/165) of mastectomy patients compared to 30% (57/192) of BCT patients (p < 0.01). Of the 75 mastectomy patients with 1-2 total positive lymph nodes after completion ALND, 44% received NRI. Women undergoing mastectomy were significantly more likely to receive both ALND and NRI than women undergoing BCS (45% vs 6%, p < 0.01). CONCLUSION: Young cT1-2N0 breast cancer patients found to have 1-3 SLN metastases received ALND, NRI, and combined ALND/NRI more frequently if they elected mastectomy over BCT. Use of both ALND and postmastectomy radiotherapy (PMRT) in this population could be reduced in the future by omitting ALND in patients for whom the need for PMRT is clear with the finding of 1-2 SLN metastases.

[Clinical outcomes of different irradiation ranges in definitive intensity-modulated radiotherapy for esophageal cancer].

Objective: To explore the therapeutic efficacy and safety of elective nodal irradiation (ENI) and involved field irradiation (IFI) in intensity-modulated radiotherapy for esophageal cancer, screen the patients suitable to undergo ENI radiotherapy and provide evidences for individual treatment of esophageal cancer. Methods: A retrospective analysis was performed on the clinical data of 924 patients with esophageal cancer who received definitive intensity-modulated radiotherapy in our hospital from January 2006 to December 2015. Among them, 272 patients received ENI and the other 652 patients received IFI. The clinicopathologic characteristics of 272 cases in ENI group and 652 cases in IFI group, who were recruited according to the balance of propensity score matching method, were compared. The Kaplan-Meier method was used to calculate 1-year, 3-years and 5-years local-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS) rates. The univariate and multivariate analysis of prognostic factors were also determined by Cox proportional hazard model and Long-rank test. Results: The clinicopathologic characteristics of these two group were not significantly different (P>0.05). The median follow-up time was 85.9 months and the follow-up rate was 95.9%. The 1-year, 3-years, 5-years PFS rates of the ENI groups were 65.3%, 31.7%, 18.4%, respectively, higher than 54.0%, 20.9%, 12.7% of the IFI group (P=0.001). The 1-year, 3-years, 5-years OS rates of the ENI groups were 79.0%, 43.7%, 24.9%, respectively, higher than 75.0%, 31.8%, 17.2% of the IFI group (P=0.003). In multivariate analysis, the sex, tumor volume, N stage and radiation field were independent factors for PFS and OS (P<0.05). Subgroup analysis showed that patients with male, age≤66 year, cervical and upper-thoracic location, tumor length≤6 cm, T1-2 stage, N0-1 stage, Ⅰ-Ⅱ stage, tumor volume≤50 cm(3), dosage>60 Gy and≤2 cycles of chemotherapy in the ENI group had a better survival rate than those in the IFI group (P<0.05). The total failure rate, local-regional failure rate in ENI group were significantly lower than those of IFI group (P=0.001, P=0.004). The incidence of bone marrow depression≥ grade 2 and 3 in ENI group was higher than that of the IFI group (P<0.05). However, the incidences of radioactive esophagitis≥ grade 3, radioactive pneumonia and late adverse reactions were not significantly different between these two groups (P>0.05). Conclusion: Compared with IFI, ENI can significantly improve the long-term survival for young, early TN stage and cervical/upper-thoracic esophageal cancer patients underwent chemotherapy.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Middle or Lower Esophageal Cancer Using Elective Nodal Irradiation: Comparison with 3D Conformal Radiotherapy.

We investigated the feasibility of simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) using elective nodal irradiation (ENI) for middle or lower esophageal cancer and compared it with three-dimensional conformal radiotherapy (3D-CRT). The study included 15 patients. The prescribed doses included a standard dose (50.4 Gy) and a high dose (60 Gy) for the planning target volume (PTV) of the involved lesions. The objective of the whole lung volume receiving ≥ 20 Gy (V20Gy) was < 30%, and the mean lung dose (MLD) was < 20 Gy. The volumes of the lung receiving 5 Gy (V5Gy) and the heart receiving 30-50 Gy (V30-50Gy) were kept as low as reasonably achievable. As a result, SIB-VMAT showed superior dose conformity for the PTV (p<0.001). Although the lung V5Gy was significantly increased (p<0.001), the V20Gy and MLD showed no significant increase. The heart V30-50Gy showed a > 20% reduction in the mean against 3D-CRTs. Our results demonstrate the feasibility of SIB-VMAT for the treatment of middle or lower esophageal cancer with ENI. Although attention should be paid to the low-dose area of the lungs, SIB-VMAT would be a promising treatment option with improved outcomes for esophageal cancer.

Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities.

PURPOSE: The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer. METHODS: An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques. RESULTS: Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%). CONCLUSION: The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

Neoadjuvant chemotherapy for breast cancer-background for the indication of locoregional treatment.

Neoadjuvant chemotherapy (NACT) has been widely adopted into the multidisciplinary management of breast cancer. The prognostic impact of treatment response has been clearly demonstrated. However, the impact of treatment response on the indication for adjuvant radiotherapy is unclear. This review summarizes important implications of NACT and treatment response on the risk of recurrence and locoregional multidisciplinary management from the standpoint of radiation oncology.

Management of the axilla after neo-adjuvant chemotherapy for breast cancer: Sentinel node biopsy and radiotherapy considerations.

Preoperative or neo-adjuvant chemotherapy in the management of breast cancer is a treatment approach that has gained in popularity in recent years. However, it is unclear if the treatment paradigms often employed for patients treated with surgery first hold true for those treated with preoperative chemotherapy. The role of sentinel node biopsy and the data supporting its use is different for those with clinically negative and clinically positive nodes prior to chemotherapy. For clinically node-negative patients, sentinel node biopsy after neo-adjuvant chemotherapy may be appropriate. For those node-positive patients whose axillary disease resolves clinically, the false-negative rate of the sentinel node biopsy is high. However, there are measures that can reduce that rate. After surgery, the radiation oncologist is often faced with complicated decisions surrounding the optimal radiotherapy in this setting. Tailoring radiation plans based on chemotherapy response holds promise and is the subject of ongoing clinical trials. In the accompanying article, we review the current literature on both surgery and radiation in axillary management and describe the interplay between these two treatment modalities. This highlights the need for multidisciplinary management in making treatment decisions for patients treated in this manner.

The role of para-aortic nodal irradiation in cervical cancer.

The current standard of care for locally advanced cervical cancer is whole pelvis and para-aortic radiation when indicated, delivered concomitantly with chemotherapy and brachytherapy. Para-aortic node involvement is a predictor of survival in locally advanced disease but presence of metastases is difficult to determine because the currently available imaging methods lack enough sensitivity to be able to detect accurately para-aortic metastases when surgical staging is not feasible. The objective of this review is to describe the current status of para-aortic lymph node irradiation in locally advanced cervical cancer. It includes analysis of the diagnostic imaging and surgical approaches for assessment of para-aortic lymph node dissemination, together with indications for radiotherapy and radiotherapeutic techniques.

Long-term outcome of concurrent chemoradiotherapy with elective nodal irradiation for inoperable esophageal cancer.

Elective nodal irradiation (ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation (CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus two concurrent cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis. Of these patients, 51 were treated with ENI, whereas 38 were treated with CFI. For the per-protocol population, the patients in the ENI group significantly improved in terms of their 10-year disease-specific overall survival (43.1% vs 10.5%, P = 0.019), 10-year disease-free survival (36.7% vs 10.2%, P = 0.040) and 10-year local recurrence-free survival (47.2% vs 17.2%, P = 0.018) compared with the CFI group. Aside from radiation esophagitis, the incidence of grade 3 or greater acute toxicities did not differ between the two groups. Multivariate analysis showed that radiation field, tumor length and clinical stage were independent prognostic factors associated with OS. Concurrent chemoradiotherapy with ENI improves both disease-specific overall survival and loco-regional control in patients with inoperable esophageal cancer receiving per-protocol treatment. The regimen has a manageable tolerability profile.