Nodal Irradiation Research Articles

Definitive Chemoradiation with Concurrent Carboplatin and Paclitaxel for HPV-Mediated Oropharyngeal Cancer (p16+ OPSCC): Survival and Local Control

Standard therapy for locally advanced p16+ OPSCC with cisplatin and bilateral nodal RT results in substantial acute and late toxicities. De-intensification strategies are under active investigation, including the de-escalation of RT dose and field size and use of less toxic RT sensitizing agents. We present our single-institution experience with definitive chemoRT using weekly carboplatin and paclitaxel and modified RT. A retrospective review of 139 consecutive patients with non-metastatic p16+ OPSCC treated with definitive chemoRT from 2013 to 2019 was performed. IMRT dose ranged from 60 to 70 Gy (median 69.96 Gy) to gross disease and 44 to 59.4 Gy (median 54.45 Gy) to elective nodal sites. Modified RT included dose reduction from 70 Gy EQD2 to 60-67.8 Gy EQD2 (2.0-2.2 Gy/fraction) and/or field modified contralateral neck. All patients received concurrent weekly paclitaxel (30 mg/m2) and carboplatin (AUC 1); 34 (24.5%) received induction chemotherapy. Patients were classified as low or intermediate risk based on HPV status, smoking history, and nodal staging per RTOG 0129 risk stratification. OS, local and regional RFS, and DSS were estimated using Kaplan-Meier method. Median FU was 40.5 months. Of 139 pts, 96 were low and 43 were intermediate risk. Median age 61 yrs (range, 40-81 yrs). 125 pts were male and 14 were female. TNM staging: 29 pts (20.9%) were T1 (22 N1, 7 N2), 68 (48.9%) T2 (4 N0, 52 N1, 12 N2), 27 (19.4%) T3 (5 N0, 15 N1, 7 N2), and 15 (10.8%) T4 (2 N0, 2 N1, 10 N2, 1 N3). Median smoking history of 22.5 pack-yrs (range, 0.25-150 pack-yrs); 59 never smoked. LR recurrence was noted in 6/96 (6.3%) low risk and 7/43 (16.3%) intermediate risk pts. DM developed in 11/96 (11.5%) low risk and 8/43 (18.6%) intermediate risk pts. Synchronous LR recurrence and DM were noted in 1/96 (1%) low risk and 2/43 (4.7%) intermediate risk pts. The 3-year LRC was 93.6% (95% CI, 86.3-97.1) in the low-risk and 77.8% (95% CI, 61.4-87.8) in the intermediate-risk group. The 3-year OS was 95.4% (95% CI, 88.3-98.3) in the low-risk and 77.6% (95% CI, 61.3 to 87.7) in the intermediate-risk group. The 3-year DSS was 96.6% (95% CI, 89.7-98.9) in the low-risk and 86.8% (95% CI, 71.0-94.3) in the intermediate-risk group. Definitive chemoRT for p16+ OPSCC with concurrent carboplatin and paclitaxel and a modified RT regimen designed to minimize acute and late effects of therapy demonstrated comparable outcomes to standard cisplatin-based chemoRT, such as report on RTOG 0129, with a high rate of LRC at 3 years. Our analysis suggests a role for a less intensive regimen using paclitaxel and carboplatin as a less toxic, effective alternative to cisplatin in the curative management of p16+ OPSCC, particularly in low-risk patients. Strategies for combating distant metastases are needed. Toxicity analysis planned to be presented separately.

Focal Boosted IMRT Treatment of Prostate Cancer to 84 Gy in 28 Fractions: Preliminary Clinical Outcomes and Dosimetry

The FLAME trial reported that focal boosting of prostate tumor to 95 Gy in 35 fractions improves biochemical control. However, this treatment is not commonly used in the United States. We investigated a focally boosted treatment of 84 Gy in 28 fractions (EQD2 108 Gy, BED 252 Gy). Between 2019-2022, men with unfavorable intermediate risk (uIR) and high risk (HR) prostate cancer were enrolled on a prospective registry and received a novel IMRT regimen. The dose levels were 84 Gy to the gross tumor volume (GTV) as defined on mpMRI (T2W and ADC) with no added margin, 70 Gy to the prostate and proximal seminal vesicles, and optional 50.4 Gy to elective pelvic lymph nodes (all 28 fractions). Patients received fiducial markers and hydrogel spacer. The treatment planning goal was to cover 95% of the GTV at 84 Gy, and also meet the target and normal tissue dosimetry criteria of the hypofractionated treatment arm of NRG-GU005. VMAT was used for treatment delivery. ADT was given at the discretion of the treating physician. A total of 20 men were included in the study, 2 (10%) uIR and 18 (90%) HR. 9 (45%) tumors were GS 7, 7 (35%) were GS 8, and 4 (20%) were GS 9. There were 13 (65%) stage cT1, 4 (20%) cT2 and 3 (15%) cT3. One (5%) patient received short term ADT, 18 (95%) long term ADT, and 1 (5%) refused ADT. 18 (90%) men received elective nodal radiation. The mean baseline PSA was 25.1 (range 4.2-73.4). The median baseline IPSS score was 11.1 (IQR 4.5-12), and 4 patients had severe baseline urinary symptoms (IPSS ≥20). The mean baseline prostate volume was 57.4 cc (range 26.8-198.3). The mean volume of the 84 Gy boost target was 7.1 cc (range 2.3-15.0) and the mean proportion of the prostate boosted was 14.8% (range 2% - 47%). There were 10 (50%) men with 1 boost target, 6 (30%) with two, 3 (15%) with three, and 1 (5%) had 4 boost targets. Targets were located in peripheral zone (85%), transition zone (30%), and central zone (5%). Patients met all per-protocol normal tissue criteria of NRG-GU005, except for bladder D0.03cc. The mean±SD (Gy) rectum D15%, D25%, and D30% were 51±5, 45±5, 42±4. The mean±SD (Gy) bladder D0.03cc, D30%, D50% were 79±4, 50±8, 38±10. At a median follow up time of 21.3 months (range 7.1-38.2), no patients have developed biochemical progression, local recurrence, distant progression, or death from prostate cancer. One patient died at 18 months from metastatic colorectal cancer, unrelated to prostate cancer treatment. Acute grade 1-2 GU toxicity occurred in 13 (65%) patients, and acute grade 1-2 GI toxicity occurred in 4 (20%) patients. No patients developed grade 3+ acute or late GU or GI toxicity. Two patients required temporary foley catheter for obstruction during RT, and both had IPSS >20 at baseline. The patient who refused ADT had a PSA bounce of magnitude 2.2 ng/mL at 14 months, PSA values declined without additional treatment. A novel 28-fraction focal boosted IMRT treatment is feasible and has an acceptable early toxicity profile. Oncologic results are promising but require longer follow up.

Is it the Type of Axillary Surgery or the Number of Removed Lymph Nodes That Increases the Risk of Breast Cancer Related Lymphedema (BCRL)? Results from a Prospective Screening Trial

Axillary surgery has been identified as the main risk factor for BCRL regardless the delivery of regional nodal radiation (RLNR). Yet it remains unknown if it is the type of axillary surgery or the number of removed lymph nodes (LN) that increases BCRL risks. Between 2008 and 2021, 3,350 patients (pts) who received surgery for breast cancer were enrolled in a lymphedema screening trial. Patients with bilateral breast cancer or without axillary surgery were excluded. Perometry was used to assess limb volume preoperatively in all patients. BCRL was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. The cohort was divided by axillary surgery type: axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). Radiation was delivered using 3D conformal technique and RLNR was defined as the usage of anterior supraclavicular field. No hypofractionation was used and doses ranged between 50 and 50.4 Gy in 25-28 fractions. Multivariable Cox proportional hazard models compared the cumulative incidence of BCRL and local failure between different patient groups. After applying inclusion criteria, 2,623 pts were available with overall median follow-up s of 6.1 years. Of the entire cohort, 709 (27%) had ALND with a median of 16 LN removed, while 1,914 (73%) received SLNB only with a median of 2 LN removed. The median number of malignant LN and patients receiving RLNR was higher in ALND group compared to SLNB only group. Frequency distribution analysis showed that the main overlap between ALND and SLNB only groups happen in the range of 3-11 LN removed. Therefore, the primary analysis focused only on pts with 3-11 LN across both groups (n = 690: ALND n = 140, SLNB n = 550). The multivariable model adjusted for BMI, RLNR, age and breast surgery showed that in this group with 3-11 LN removed in both cohorts, ALND remained significantly associated with BCRL (HR: 4.2, p<0.0001). Separate analyses for the entire SLNB only group and ALND groups were conducted to evaluate if the BCRL risk increases per each removed LN within the same axillary surgery group. The multivariable analysis for SLNB only pts(N = 1,914) showed that for each LN removed the risk of BCRL did not increase significantly (HR:1.06, p = 0.3), similarly for ALND group (N = 709) for each LN removed (HR:1.02, p = 0.08). For pts with pathologic N2-N3 disease and clinical node negative without neoadjuvant chemotherapy receiving ALND, the number of LN removed did not significantly improve neither Local control (HR:1.02, p = 0.8) nor distant disease survival (HR:1.01, p = 0.6). ALND procedure per se is the main risk factor for BCRL not the number of LNs removed. For high-risk pts with >N2 disease, aggressive ALND did not improve tumor outcome. De-escalation with targeted axillary sampling followed by RLNR should be evaluated. Future lymphedema research should account for type of axillary surgery instead of number of LNs removed as a factor. (NCT01521741).

Does Dual Anti-HER2 Therapy Increase Early Cardiac Toxicity in Comparison with Trastuzumab Alone in Breast Cancer Patients Receiving Adjuvant Radiotherapy? A Multicenter Retrospective Study

Adjuvant trastuzumab in combination with RT has proved its safety in terms of cardiac events. Dual anti-HER2 therapy with pertuzumab is currently standard adjuvant therapy in N+ and high-risk N0 early breast cancer (BC) patients. Our study aims to find if it increases early cardiac toxicity compared with trastuzumab alone in BC patients receiving adjuvant radiotherapy. Operable BC patients who received adjuvant radiotherapy (RT) and trastuzumab with or without pertuzumab between January 2017 and September 2020 in 7 Chinese centers were retrospectively reviewed. The cardiac examination included ultrasonography, electrocardiogram (ECG), NT-proBNP, and cTnI before RT and during follow-up. The cardiac event was any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT. In total, 711 patients with a median age of 52 years were included, of whom 567 (79.7%) patients were treated with trastuzumab-only and 144 (20.3%) patients received dual anti-HER2 therapy. Adjuvant RT was given concurrently in 140/144 (97.2%) of dual anti-HER2 therapy and 562/567 (99.1%) of trastuzumab alone, respectively. With a median follow-up of 11 months, no patients developed symptomatic heart diseases. Among patients with normal baseline, 17 (2.4%), 86 (12.1%), 18 (2.5%) and 14 (7.3%) developed new-onset diastolic dysfunction, left ventricular ejection fraction (LVEF) decline, abnormal ECG, and abnormal NT-proBNP, respectively. No significant difference was found between the trastuzumab-only and dual anti-HER2 cohort in the incidence of all kinds of new-onset cardiac events (all p > 0.1). Multivariate analysis showed that left-sided (vs right-sided) RT significantly increased the risk of ECG abnormality (HR = 2.32, 95% CI 1.62-3.32, p<0.001). Increased age was an independent risk factor for diastolic dysfunction (HR = 1.1, 95% CI 1.02-1.18, p = 0.0098). Dosimetric analysis showed that patients who developed any cardiac events had increased mean heart dose (397.67±251.08 vs 344.87±236.75 cGy, p = 0.032). A significant increase in risk of cardiac events was found in patients with mean heart dose > 450 cGy (HR = 1.55, 95% CI 1.17-2.05, p = 0.0024), V5 > 26% (HR = 1.51, 95% CI 1.09-2.09, p = 0.013), and V30 > 5.5% (HR = 1.49, 95% CI 1.09-2.04, p = 0.0117), respectively. Further analysis was done in the subgroup of patients treated with left-sided RT, internal mammary nodes RT, or anthracyclines, no difference in risk of cardiac events was found between trastuzumab alone and dual anti-HER2 therapy in concurrent with RT (all p > 0.05). Compared with trastuzumab-only, dual anti-HER2 therapy does not increase early cardiac toxicity in combination with adjuvant RT in BC patients. Cardiac radiation exposure remains the primary risk factor associated with early cardiac toxicity.

Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67months and OS of 110months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

AimThe optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.MethodsThis retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.ResultsThree hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.ConclusionFavorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Abstract IA05: Nodal and systemic Immune effects of radiation in HNSCC

Abstract When combined with immunotherapy, HPV-unrelated HNSCC has a high incidence of local and regional recurrence. Since nodal metastasis remains a common pattern of spread for HNSCC, elective nodal irradiation (ENI) is commonly employed to eradicate potential microscopic disease in non-involved lymph nodes. Given our developing understanding that (1) immune cells are highly radio-sensitive, and (2) that anti-tumor T cell priming, and expansion, occur in the draining lymph nodes (DLNs), we tested whether RT directed at gross tumor only could increase the effectiveness of immunotherapies. Using preclinical models and samples from canine and human trials, we tested the effects of RT with or without ENI. Immune cell differences in the tumor tissue, DLNs, and blood were characterized with flow cytometry. We found that tumor only irradiation decreased local and distant tumor growth and increased survival but increased regional recurrence. Sentinel lymph node resection or irradiation was effective at reducing regional metastasis. We show that the effectiveness of tumor only RT is likely mediated via induction of a systemic immune response dependent on antigen recognition by T cells in the DLNs. These data support the hypothesis that effective anti-tumor immunotherapy treatment requires a systemic, antigen-dependent immune response which is primed in the DLNs. Citation Format: Laurel B. Darragh, Jacob Gadwa, Keara Boss, Sana D. Karam. Nodal and systemic Immune effects of radiation in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr IA05.

Primary tumor site for localized Merkel cell carcinoma drives different management strategies without impacting oncologic outcomes

Background and purposeClinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era. Materials and methodsPatterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014–2021. ResultsOf 80 patients who met inclusion criteria, the primary tumor anatomic site was head and neck (HN) for 42 (53%) and non-head and neck (NHN) for 38 (47%). Primary tumor risk factors were similar between cohorts. Fewer patients with HN tumors had wide local excision (WLE; HN-81% vs. NHN-100% p < 0.01). Of those undergoing WLE, patients with HN tumors received higher dose adjuvant RT (>50 Gy: HN-70% vs. NHN-8%; p < 0.01). Patients with HN tumors were less likely to undergo sentinel lymph node biopsy (HN-62%vs. NHN-100%; p < 0.01) and more likely to have elective nodal RT (HN-48% vs. NHN-0%). Despite varying management strategies, there was no significant difference in local recurrence-free survival (3-yr LRFS HN-94% vs. NHN-94%; p = 0.97), nodal recurrence-free survival (3-yr NRFS HN-89% vs. NHN-85%; p = 0.71) or overall recurrence-free survival (3-yr RFS 73% HN vs. 80% NHN; p = 0.44). ConclusionsAmong patients with primary MCC who had RT as a component of their initial treatment strategy, anatomically-driven heterogeneous treatment approaches were associated with equally excellent locoregional disease control.

Prognostic impact of radiotherapy-induced-lymphopenia in patients treated with breast-conservative surgery

We investigated a prognostic impact of radiotherapy-induced lymphopenia (RIL) in breast cancer patients treated with breast-conservative surgery (BCS). We included 531 breast cancer patients who were treated with BCS and adjuvant radiotherapy. None of these received (neo)adjuvant chemotherapy. Pre- and post- absolute lymphocyte counts (ALC) were reviewed before and after radiotherapy. The primary endpoint was to evaluate recurrence-free survival (RFS) according to the pre-to-post ALC ratio. Binary logistic regression model was used to identify risk factors for RIL. Either continuous or categorical (> 2.4) pre-to-post ALC ratio was associated with RFS. In 531 patients receiving whole breast irradiation (WBI) and regional nodal irradiation (RNI), RFS was significantly reduced in the patients with high pre-to-post ALC ration (> 2.4). In multivariable analysis, low pre-to-post post ALC ratio was significantly related to decreased RFS in the multivariable analysis (HR 2.293, 95% CIs 1.110–4.735, P = 0.025). In 452 patients treated with WBI alone, high pre-to-post ALC ratio was still significantly associated with decreased RFS in the multivariable analysis (HR 2.708, 95% CIs 1.016–7.218, P = 0.046). In binary logistic regression analysis, RNI was only significant risk factor for clinically meaningful RIL. Our findings show that a markedly decrease in ALC during radiotherapy has a negative prognostic impact.

Patient-reported lower limb edema after primary radiotherapy for prostate cancer

Background Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. Material and methods A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. Results At a median follow-up of 15 (3–51) months, the overall crude incidence of patients reporting ‘quite a bit’ or ‘a lot’ of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of ‘quite a bit’ and ‘a lot’ of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for ‘quite a bit’ or ‘a lot’ of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported ‘quite a bit’ and 2.9% (±0.5%) reported ‘very much’ LLE (p < 0.001), respectively. Significant risk factors (p < 0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI ≥ 30 compared to normal weight patients. Conclusion Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report ‘quite a bit’ or ‘very much’ LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE.

Whole Breast Irradiation in Comparison to Endocrine Therapy in Early Stage Breast Cancer-A Direct and Network Meta-Analysis of Published Randomized Trials.

Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42-0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53-1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45-2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59-1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38-1.36; p = 0.305). Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

Elective nodal irradiation versus involved-field irradiation for stage II–IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes

BackgroundDefinitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI).Materials and methodsPatients with stage II–IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated.ResultsThe 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8–182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61–1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT.ConclusionCervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

Proton therapy for the management of localized prostate cancer: Long-term clinical outcomes at a comprehensive cancer center

Background and purposeProton therapy (PT) has emerged as a standard-of-care treatment option for localized prostate cancer at our comprehensive cancer center. However, there are few large-scale analyses examining the long-term clinical outcomes. Therefore, this article aims to evaluate the long-term effectiveness and toxicity of PT in patients with localized prostate cancer. Materials and MethodsReview of 2772 patients treated from May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 850]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 116]. Biochemical failure and toxicity were analyzed using Kaplan-Meier estimates and multivariate models. ResultsThe median patient age was 66 years; the median follow-up time was 7.0 years. Pelvic lymph node irradiation was prescribed to 28 patients (1%) (2 [0.2%] U-IR, 11 [3.5%] HR, and 15 [12.9%] VHR). The median dose was 78 Gy in 1.8–2.0 Gy(RBE) fractions. Freedom from biochemical relapse (FFBR) rates at 5 years and 10 years were 98.2% and 96.8% for the LR group; 98.3% and 93.6%, F-IR; 94.2% and 90.2%, U-IR; 94.3% and 85.2%, HR; and 86.1% and 68.5%, VHR. Two patients died of prostate cancer. Overall rates of late grade ≥ 3 GU and GI toxicity were 0.87% and 1.01%. ConclusionsProton therapy for localized prostate cancer demonstrated excellent clinical outcomes in this large cohort, even among higher-risk groups with historically poor outcomes despite aggressive therapy.

Adjuvant radiation therapy for breast cancer

Adjuvant radiotherapy is an integral part of multimodal therapy for early breast cancer. It contributes to the reduction of local recurrences across all disease stages. (Moderate) hypofractionated whole-breast irradiation is the standard of care. In low-risk situations, partial breast irradiation can be an option. The indication for adjuvant radiotherapy after mastectomy or additional irradiation of regional lymph nodes depends on the patient's individual risk profile. Long-term results of treatment and further development of irradiation techniques now allow shorter, individualized and well-tolerated treatments with the aim of therapy de-escalation.

Long-Term Patient-Reported Outcomes Comparing Oncoplastic Breast Surgery and Conventional Breast-Conserving Surgery: A Propensity Score-Matched Analysis.

Oncoplastic breast surgery (OBS) combines plastic surgery techniques with conventional breast-conserving surgery (BCS) and expands BCS eligibility. Limited data are available on patient-reported outcomes (PROs) after OBS. Here we compare long-term PROs after OBS and BCS utilizing the BREAST-Q. Women undergoing OBS or BCS between 2006 and 2019 who completed ≥ 1 long-term BREAST-Q survey 3-5 years postoperatively were identified. Baseline characteristics were compared between women who underwent OBS/BCS. Women who underwent OBS were paired with those who underwent BCS using 1:2 propensity matching [by age, body mass index (BMI), race, T stage, and multifocality]. BREAST-Q scores were compared preoperatively and 3-5 years postoperatively. A total of 297 patients were included for analysis (99 OBS/198 BCS). Women who underwent OBS were younger (p < 0.001) and had higher BMI (p = 0.005) and multifocal disease incidence (p = 0.004). There was no difference between groups in nodal stage, re-excision rates, axillary surgery, chemotherapy, endocrine therapy, or radiotherapy. After propensity matching preoperatively, women who underwent OBS reported lower psychosocial well-being (63 versus 100, p = 0.039) but similar breast satisfaction and sexual well-being compared with women who underwent BCS; however, only three patients who underwent BCS had preoperative BREAST-Q scores available for review. In long-term follow-up, women who underwent OBS reported lower psychosocial scores (74 versus 93, p = 0.011) 4 years postoperatively, but not at 5 years (76 versus 77, p = 0.83). There was no difference in long-term breast satisfaction or sexual well-being. Women who undergo OBS present with a larger disease burden and may represent a group of non-traditional BCS candidates; they reported similar long-term breast satisfaction and sexual well-being compared with women who undergo BCS. While women who underwent OBS reported lower psychosocial well-being scores preoperatively and during a portion of the follow-up period, this difference was no longer seen at 5 years postoperatively.

Axillary Management in Breast Cancer Patients Undergoing Upfront Surgery: Results from a Nationwide Survey on Behalf of the Clinical Oncology Breast Cancer Group (COBCG) and the Breast Cancer Study Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1-2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1-2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre-South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations.

Regional Nodal Irradiation and Post-Mastectomy Radiation Therapy After Up-Front Surgery

Regional Nodal Irradiation and Post-Mastectomy Radiation Therapy After Up-Front Surgery

Comparison of prone and supine positioning for breast cancer radiotherapy using REQUITE data: dosimetry, acute and two years physician and patient-reported outcomes

Objective Most patients receive whole breast radiotherapy in a supine position. However, two randomised trials showed lower acute toxicity in prone position. Furthermore, in most patients, prone positioning reduced doses to the organs at risk. To confirm these findings, we compared toxicity outcomes, photographic assessment, and dosimetry between both positions using REQUITE data. Methods REQUITE is an international multi-centre prospective observational study that recruited 2069 breast cancer patients receiving radiotherapy. Data on toxicity, health-related quality of life (HRQoL), and dosimetry were collected, as well as a photographic assessment. A matched case control analysis compared patients treated prone (n = 268) versus supine (n = 493). Exact matching was performed for the use of intensity-modulated radiotherapy, boost, lymph node irradiation, chemotherapy and fractionation, and the nearest neighbour for breast volume. Primary endpoints were dermatitis at the end of radiotherapy, and atrophy and cosmetic outcome by photographic assessment at two years. Results At the last treatment fraction, there was no significant difference in dermatitis (p = .28) or any HRQoL domain, but prone positioning increased the risk of breast oedema (p < .001). At 2 years, patients treated in prone position had less atrophy (p = .01), and higher body image (p < .001), and social functioning (p < .001) scores. The photographic assessment showed no difference in cosmesis at 2 years (p = .22). In prone position, mean heart dose (MHD) was significantly lower for left-sided patients (1.29 Gy vs 2.10 Gy, p < .001) and ipsilateral mean lung dose (MLD) was significantly lower for all patients (2.77 Gy vs 5.89 Gy, p < .001). Conclusions Prone radiotherapy showed lower MLD and MHD compared to supine position, although the risk of developing breast oedema during radiotherapy was higher. At 2 years the photographic assessment showed no difference in the cosmetic outcome, but less atrophy was seen in prone-treated patients and this seems to have a positive influence on the HRQoL domain of body image.

A review on lymphocyte radiosensitivity and its impact on radiotherapy.

It is well known that radiation therapy causes lymphopenia in patients and that this is correlated with a negative outcome. The mechanism is not well understood because radiation can have both immunostimulatory and immunosuppressive effects. How tumor dose conformation, dose fractionation, and selective lymph node irradiation in radiation therapy does affect lymphopenia and immune response is an active area of research. In addition, understanding the impact of radiation on the immune system is important for the design and interpretation of clinical trials combining radiation with immune checkpoint inhibitors, both in terms of radiation dose and treatment schedules. Although only a few percent of the total lymphocyte population are circulating, it has been speculated that their increased radiosensitivity may contribute to, or even be the primary cause of, lymphopenia. This review summarizes published data on lymphocyte radiosensitivity based on human, small animal, and in vitro studies. The data indicate differences in radiosensitivity among lymphocyte subpopulations that affect their relative contribution and thus the dynamics of the immune response. In general, B cells appear to be more radiosensitive than T cells and NK cells appear to be the most resistant. However, the reported dose-response data suggest that in the context of lymphopenia in patients, aspects other than cell death must also be considered. Not only absolute lymphocyte counts, but also lymphocyte diversity and activity are likely to be affected by radiation. Taken together, the reviewed data suggest that it is unlikely that radiation-induced cell death in lymphocytes is the sole factor in radiation-induced lymphopenia.

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI). Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient. ResultsMean heart dose was 7.9Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint<8Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (rs=–0.25, P=0.050) and between mean heart dose and CCDps (rs=0.25, P=0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant. ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.