Locoregional Radiotherapy Research Articles

Abstract GS02-07: Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304

Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast irradiation (WBI+RNI) after breast conserving surgery (BCS) is well established in pts with pathologically positive axillary nodes (pN+). Pts who present with axillary node involvement (cN+), receive neoadjuvant chemotherapy (NC), and are found to be pathologically node-negative at surgery (ypN0), have lower loco-regional recurrence (LRR) rates compared to those who remain pathologically node-positive (ypN+). This phase III, randomized trial aimed to evaluate whether CWI+RNI after mastectomy or addition of RNI to WBI after BCS significantly improves invasive breast cancer recurrence-free interval (IBC-RFI) in cN+ pts found to be ypN0 after NC. Methods: Eligible pts had clinical cT1-3, N1, M0 invasive breast cancer (biopsy-proven N+ by FNA/core needle bx), completed ≥8 wks of NC (and anti-HER2 therapy if HER2+), and were ypN0 after mastectomy or BCS and sentinel node biopsy (SLNB, ≥2 nodes), axillary lymph node dissection (ALND), or both. Pts were randomized to “No RNI” (i.e., observation after mastectomy or WBI after BCS) vs. “RNI” (i.e., CWI+RNI after mastectomy or WBI+RNI after BCS). Primary endpoint was IBC-RFI. Secondary endpoints reported here: LRR-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS). Study was designed to have 80% power to detect 35% reduction in annual rate of IBC-RFI for an absolute risk reduction of 4.6% (5-yr cumulative rate). Per protocol, final analysis was to occur after 172 events or 10 yrs after study initiation.Here we report the time-driven analysis prespecified in the protocol. Results: From 9/13-12/20, 1,641 pts were enrolled; 1,556 pts were available for primary event analysis; median f/u time 59.5 mos (IQR 40.7-74.1). Pt/tumor characteristics were well balanced between groups. Median age 52 yrs (range 21-84); 31% non-white; 21% cT1, 60% cT2, 19% cT3; 23% triple-negative, 21% HR+/HER2-, 56% HER2+; 58% BCS; 55% SLNB, 45% ALND+/-SLNB; and 78% had breast pathologic complete response. At the time of the analysis, 109 IBC-RFI events (63% of the planned 172) were confirmed (“No RNI”: 59, “RNI”: 50). There was no statistically significant difference between groups for IBC-RFI (HR=0.88, 95%CI 0.60-1.29; p=0.51), 5-yr point estimates: 91.8% for “No RNI” and 92.7% for “RNI.” There were no statistically significant differences between the treatment groups for secondary endpoints. There were no study-related deaths and no unexpected toxicities.Grade 4 toxicity was rare (0.1% with “No RNI”, 0.5% with “RNI”); 6.5% of pts developed grade 3 toxicity in “No RNI” and 10% in “RNI” group. Most common grade 3 toxicity was radiation dermatitis (3.3% in “No RNI,” 5.7% in “RNI”). Conclusion: In pts who present with biopsy-proven axillary node involvement and convert their axillary nodes to ypN0 after NC, CWI+RNI after mastectomy, or WBI+RNI after BCS, did not significantly improve IBC-RFI, LRRFI, DRFI, DFS, or OS. These findings suggest that downstaging involved axillary nodes with NC can result in optimization of adjuvant radiotherapy without adversely affecting oncologic outcomes. Follow-up of pts for long-term outcomes continues. NCT01872975 *EPM and JW are co-first authors. Table 1 Citation Format: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Nilendu Gupta, X. Allen Li, Peter Lucas, Nadeem Abu-Rustum, Saumil Gandhi, Rahul Tendulkar, Robert Coleman, Keiichi Fujiwara, Samantha Seaward, William Irvin, Kristin Higgins, Robert Mutter, Jean-Francois Boileau, Andrew Muskovitz, Reshma Jagsi, Anna Weiss, Curran Walter Jr., Norman Wolmark. Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-07.

Abstract PO1-03-05: Tolerance of adjuvant radiotherapy combined with pembrolizumab for triple negative breast cancer

Abstract BACKGROUND AND PURPOSE: The current standard-of-care management of locally advanced triple negative breast cancer (TNBC) is based on neoadjuvant chemo-immunotherapy with pembrolizumab, surgery, radiotherapy and adjuvant pembrolizumab. However, the safety of combining pembrolizumab with adjuvant breast radiotherapy has never been evaluated. This study evaluated the tolerance profile of concurrent pembrolizumab (P) with adjuvant radiotherapy (RT) in locally advanced TNBC patients. METHODS: This bicentric ambispective study included the first prospectively registered patients with non-metastatic TNBC treated with the KEYNOTE-522 regimen in our institution. They received P in combination with carboplatin and paclitaxel chemotherapy and a second chemotherapy with doxorubicin and cyclophosphamide, followed by surgery and locoregional RT with or without P as adjuvant treatment. RT was normo- or hypofractionated, for the breast or chest wall, with or without lymph node irradiation according to institutional guidelines. Adjuvant P was administered at a total dose of 1800 mg at 200 mg once every 3 weeks or 400 mg once every 6 weeks. The safety profile was evaluated during and after the end of RT (until the last contact) with CTCAE V.5 scale. RESULTS: A total of 55 patients (pts) were prospectively included between July 2021 and March 2023. The median age was 49 years (29-69). The median follow-up was 12 months ( range, 10-26). Of them, 27 (49%) did not receive P concomitantly with RT (RT-only group) because of neo-adjuvant treatment related toxicities, and 28 (51%) received P concomitantly with RT (P-RT group). There was no statistical difference in population and toxicity between the RT-only group and the P-RT group. Nine patients were diagnosed with cardiac toxicities before the beginning of the RT and did not receive P during the RT. No RT-induced grade ≥4 toxicities were observed. Early toxicities were mainly grade 1-2. Two grade 3 toxicities occurred (1 case of axillary pain in the P-RT group and 1 radiodermatitis in the RT-only group). No cardiac or pulmonary toxicities ≥grade 2 were observed with adjuvant therapy. The toxicity profile is given in table 1. DISCUSSION: In these series, the main cause of discontinuation of pembrolizumab was related to suspicion of cardiac adverse events occurring during the neoadjuvant treatment and related to the injection of pembrolizumab or of the chemotherapy. All myocarditis happened before radiotherapy and did not affect the administration of radiotherapy. In this context, the optimal radiotherapy technique and cardiac dose constraints after ICI-induced myocarditis is unknown and late cardiotoxicity studies will be needed to precise these points. Cardiac sparing techniques, such as deep-inspiration breath hold, proton therapy, or alternative positioning (such as isocentric lateral decubitus) could be considered. CONCLUSION: Adjuvant radiotherapy can be combined with pembrolizumab for TNBC patients without increasing the risk of radiation-induced adverse events, allowing maintaining a systemic treatment in these high-risk patients. Longer follow-up and prospective studies are needed to validate these results. Adjuvant treatment-related adverse events Citation Format: Youlia Kirova, Thaïs Tison, Pierre Loap, Emilie ARNAUD, Kim Cao, Solène Bringer, Manon Kissel, Safia Maaradji, Juliette Mainguene, Jean-Yves Pierga, Florence Lerebours, Anne Salomon, Mariana Mirabelle, Delphine Loirat, Francois-Clement Bidard. Tolerance of adjuvant radiotherapy combined with pembrolizumab for triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-05.

Abstract PO5-19-10: First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients

Abstract Objective Normofractionated (NF) radiation therapy (RT) is still standard for loco-regional early breast cancer (EBC) in many countries. HypoG-01, a UNICANCER, non-inferiority, open-label, multicenter, randomized phase III trial (NCT03127995), conducted in parallel with the DBCG Skagen trial 1 (NCT02384733), evaluated hypofractionated (HF) RT with 40 Gy/15 fr (2.67 Gy/fr) versus NF RT 50 Gy/25 fr (2.0 Gy/fr). This is the first report of oncological outcomes, secondary endpoints of the trial. Methods Patients (pts) ≥18 years old were operated for T1-3, N0-3, M0 breast cancer. All pts received nodal and thoracic wall or breast RT. Tumor-bed boost (sequential or simultaneous) and nodal levels treated were decided according to local guidelines. Target volumes were delineated according to the ESTRO consensus. RT technique was left at the investigator’s discretion. Stratification factors included treating center, type of surgery, number of positive nodes and body mass index. The primary endpoint, reported previously, was time to occurrence of arm lymphedema. Oncological outcomes included locoregional relapse free survival (LRFS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS) as defined per DATECAN guidelines. All time to cancer related endpoints were defined as starting from the date of randomization until the event. The primary statistic test was stratified one-sided logrank test: 5% significance level in per-protocol population (PPP) with a pre-specified non-inferiority margin of 1.545. Stratified Cox model was used for calculating hazard ratios of oncological outcomes. Results In total, 1265 pts were randomized to HF versus NF RT from Sep 2016 to Mar 2020 with 1221 in the PPP (HF group 614 pts (50.3%); NF group 607 (49.7%)), 5 consent withdrawn and 39 major deviations. Median age was 58 years (range 23-91), surgery included mastectomy (501 pts; 45%) and axillary clearance (921 pts; 82.8%). Sequential (67.8%) or simultaneous integrated (32.2%) tumor-bed boost was used in 596 pts (48.8%). With a median follow-up for OS in PP analysis of 3.8 years (95% CI 3.3 to 3.9), HF was non-inferior to NF RT in terms of lymphedema (HR=1.07; 90% CI 0.86-1.34, non-inferiority p=0.003). Table 1 reports the hazard ratio and 3-year survival rates for the oncological endpoints LRFS, IDFS, DDFS, BCCS and OS. There was no sign of disadvantage for any of these endpoints comparing HF to NF. Additional analyses will be presented at the meeting. Conclusion Moderately HF loco-regional RT is non-inferior to NF RT in terms of lymphedema risk in EBC and does not show a disadvantage in terms of LRFS, IDFS, DDFS, BCCS and OS with a median follow-up of 3.8 years. Together with the Skagen 1 trial, this study provides level 1A evidence supporting the use of 40 Gy/15 fr for loco-regional radiation therapy in EBC with respect to arm lymphedema risk; Table 1: Oncological outcomes according to treatment arm in the per protocol analysis HF: Moderately hypofractionated radiation therapy; NF: Normofractionated radiation therapy; n:number of patients; N: number of events Citation Format: Sofia Rivera, Eleni Karamouza, Youlia Kirova, Séverine Racadot, Mohamed Benchalal, Jean-Baptiste Clavier, Claire Charra-Brunaud, Marie-Eve Chand-Fouche, Delphine Argo-Leignel, Karine Peignaux, Ahmed Benyoucef, David Pasquier, Philippe Guilbert, Julien Blanchecotte, Agnès Tallet, Adeline Petit, Guillemette Bernadou, Xavier Zasadny, Claire Lemanski, Jacques Fourquet, Emmanuelle Malaurie, Honorine Kouto, Carole Massabeau, Alexandre Henni, Pauline Regnault, Aurélie Belliere, Yazid Belkacemi, Magali Le Blanc-Onfroy, Julien Geffrelot, Jean-Briac Prevost, Marie Bergeaud, Assia Lamrani-Ghaouti, Amandine Ruffier, Naima Bonnet, Stephanie Wong, Christine Rossier, Thomas Brion, Pierre Maroun, Claire Petit, Guillaume Auzac, Stefan Michiels. First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-10.

Abstract PO4-20-09: Successful outcome of locally advanced HR+HER2+ breast cancer treatment in a young female after pancreas-kidney transplantation. 3-year follow-up

Abstract Background Solid organs recipients with subsequent cancer comprise a group of patients with unmet medical needs: they lack any clinical trials or guidelines for treatment. There are only individual case reports in literature. Meanwhile their number is growing due to achievements in transplantology and improved cancer diagnosis. Case presentation А young 34-year-old female attended our center in September 2019 with a palpable mass and peau d'orange of the left breast. A core-needle biopsy of the left breast mass revealed invasive ductal carcinoma G3, estrogen receptor 7 (Allred), progesterone receptor 6 (Allred), HER-2 (3+), Ki-67 49%. Left axillary lymph node biopsy revealed metastatic breast cancer. After a complete examination the clinical stage was cT4bN1fM0, IIIB stage. The patient had a history of Type 1 diabetes mellitus since 2003 leading to multiple complications including terminal diabetic nephropathy, which required renal replacement therapy with the use of long-term hemodialysis since July 2014. The other complications consisted of severe retinopathy with corneal transplantation on the left eye in April 2013, an episode of right eye hemophthalmia in March 2016 with consequent loss of vision in the right eye, polyneuropathy, gastropathy and enteropathy. The patient underwent a simultaneous pancreas-kidney transplantation in April, 2016 and was on permanent immunosuppressive therapy with tacrolimus 8 mg daily and methylprednisolone 8 mg daily. The function of both transplants was satisfactory. This unique case was published by Pinchuk A. et al. in Transplant Proceedings, 2017 [doi: 10.1016/j.transproceed.2017.10.005]. A multidisciplinary approach was applied to tailoring treatment plan for this patient. Initially immunosuppressive therapy was modified: the patient discontinued methylprednisolone and started everolimus with simultaneous tacrolimus dose reduction (their doses adjusted according to blood concentrations). The tumor board decision was to start neoadjuvant therapy with regimen with the mildest and the most manageable toxicity profile and to avoid anthracyclines. From October to December 2019 the patient received 12 cycles of paclitaxel 80 mg/m2 day 1 weekly and 4 cycles of anti-HER2 dual blockade: trastuzumab 8 mg/kg day 1 followed by 6 mg/kg day 1 every 21 days + pertuzumab 840 mg day 1 followed by 420 mg day 1 every 21 days. Adverse events were: stomatitis grade 1, palmar-plantar erythrodysesthesia grade 1, diarrhea grade 2. Partial response was evaluated in the end of December 2019, but due to persistent skin edema, she was not a candidate for surgical treatment. The tumor board decision was to proceed with T-DM1 + pertuzumab based on the results of the KRISTINE trial [doi:10.1016/s1470-2045(17)30716-7]. From January to March 2020 the patient received 4 cycles of trastuzumab-emtansine 3,6 mg/kg day 1 every 21 days + pertuzumab 420 mg day 1 every 21 days. The patient tolerated this treatment with mild toxicity: ALT & AST increase grade 2 and diarrhea grade 2. Considering that the edema was significantly reduced, surgical treatment was planned. The patient underwent a modified radical mastectomy for left breast cancer on 14 of April 2020. The pathological stage was ypT1аN0 R0, RCB I. The patient continued trastuzumab emtansine until November 2020 (up to 1 year of anti-HER2 targeted therapy) in the adjuvant setting. In June 2020 she underwent locoregional radiation therapy. Tamoxifen with ovarian function suppression (LHRH agonists) for 5 years was started in June 2020. Fortunately, after 3 years of follow-up after surgery there is no evidence of disease and no delayed cancer treatment complications. Conclusion: Personalized multidisciplinary team decisions for cancer patients after organ transplantation are crucial to further improve the long-term outcome of these patients. Citation Format: Lyudmila Zhukova, Natalya Polshina. Successful outcome of locally advanced HR+HER2+ breast cancer treatment in a young female after pancreas-kidney transplantation. 3-year follow-up [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-09.

Abstract PO5-03-09: Concurrent versus sequential use of adjuvant capecitabine and radiation in patients with triple-negative breast cancer with residual disease: A retrospective review

Abstract Background: The CREATE-X trial demonstrated benefit of adjuvant capecitabine for patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy and surgery. In clinical practice however, physician discretion determines the sequence of capecitabine relative to radiation therapy (RT), as well as the treatment dose. Therefore, our study aimed to assess the treatment patterns and tolerance of capecitabine and RT in patients with residual TNBC at our institution after publication of the CREATE-X study. Methods: This was a retrospective IRB-approved study that included patients with TNBC who had residual disease following neoadjuvant chemotherapy and surgery and received both adjuvant loco-regional RT and capecitabine at our institution between July 1, 2017 and June 30, 2021. Patient characteristics and treatment regimens were abstracted from medical charts. For this study, we defined optimally-delivered capecitabine to be a starting dose of 1250 mg/m2 twice per day on days 1-14 every 3 weeks as per the CREATE-X trial, and all planned cycles completed without dose reductions or discontinuation. RT was defined as optimally delivered when patients completed the prescribed dose without a treatment break of > 1 week or discontinuation of planned RT. We used descriptive statistics to report our observations. Results: Thirty-four patients met our eligibility criteria. The median age at diagnosis was 56 years (range: 30-77 years) and the median follow up time was 48 months. Of the 27 patients who received sequential RT and capecitabine, the median starting dose of capecitabine was 1000 mg/m2. Of the 7 patients who received concomitant RT and capecitabine, the median starting dose during RT was 800 mg/m2; after completion of RT, patients completed 6 additional cycles of capecitabine at a median dose of 1000 mg/m2. We observed a greater residual breast tumor burden in patients prescribed concomitant RT and capecitabine; 71.4% were ypT2/T3 compared to only 18.5% ypT2/T3 in sequentially treated patients (OR 11.0; 95% CI, 1.64 to 73.97; p=0.05). There was no significant difference in the positive lymph node status between the 2 groups (42.9% and 40.7%, respectively). A median RT dose of 50 Gy in 25 fractions was delivered in both schedules. No patients discontinued RT due to intolerance. In the 27 sequentially treated patients, the majority (73%) received RT before capecitabine. Among these, 14 patients (51.9%) required a dose reduction and 6 patients (22.2%) discontinued capecitabine due to intolerance. Of the 7 patients receiving concomitant RT and capecitabine, 2 patients (28.5%) discontinued capecitabine due to intolerance (one during RT and one following completion of RT). The concomitant RT and capecitabine regimen was not associated with higher odds of prematurely discontinuing capecitabine compared to the sequential schedule (OR 1.15; 95% CI, 0.18 to 7.34). Conclusion: In this study, most patients received a sequential schedule and those with a higher residual disease burden were more likely to be prescribed concomitant RT and capecitabine. The starting dose of capecitabine in both schedules was lower than the starting dose in the CREATE X trial but consistent with the practice standard in the US. Our early experience did not demonstrate any signal to suggest a difference in the tolerance of capecitabine administered sequentially or concurrently. Further studies are needed to evaluate the optimal sequence of RT and capecitabine in the adjuvant setting. Citation Format: Catherine Yu, Alaina Kessler, Theresa Shao, Sarah Cate, Paula Klein, Manjeet Chadha. Concurrent versus sequential use of adjuvant capecitabine and radiation in patients with triple-negative breast cancer with residual disease: A retrospective review [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-09.

3131: Development of an automated VMAT-technique for left locoregional breast radiotherapy including IMN

3131: Development of an automated VMAT-technique for left locoregional breast radiotherapy including IMN

2553: Locoregional hypofractionated radiotherapy and T-DM1 in breast cancer: a single center experience

2553: Locoregional hypofractionated radiotherapy and T-DM1 in breast cancer: a single center experience

DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control “always” matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Early Recurrence Adenoid Cystic Carcinoma of Paranasal Sinus, A Case Report

Introduction: Adenoid cystic carcinoma (ACC) of the head and neck is a rare salivary gland tumor. It grows and spreads in silence until causing a symptom. Surgery is still the main treatment of choice although complete resection is hard to achieve most of the time. Case Presentation: This report presents an adult female with ACC of the left hard palate and left maxillary sinus, this patient also had slight lymph nodes enlargement. She underwent sub-total maxillectomy followed by locoregional radiotherapy. The tumor spreads out to vertebral bones within one year and keeps on progressing despite bone radiation. It recurred locally and appeared in the neck lymph node 2 months after bone metastasis. Lung metastasis happened 3 months later and soon she passed away. Mortality happened in less than two years after initial treatment. Conclusion: : High tumor grade, advanced T stage, lymph node involvement, perineural invasion, and paranasal sinus location clearly define poor prognostic factors. In this case, adjuvant radiotherapy for poor prognostic factors ACC doesn’t give any benefit in locoregional control or overall survival.

Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; aquestionnaire addressing 11major symptoms and wellbeing on anumeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported ahigher symptom burden (mean 30 versus20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean18), followed by those on Her-2-targeting agents without chemotherapy (mean19), those on chemotherapy with or without other drugs (mean26), and those without systemic therapy (mean41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus1.8, p = 0.03) and atrend towards lower depression scores, p = 0.09. Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial

Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p=0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p=0.004). The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. This study was funded by Science and Engineering Research Board (SERB), India.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results

PurposeModerate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methodsA prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. ResultsWith a median follow-up of 19 months (range 1–49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. ConclusionsOne-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

Surface-guided radiotherapy systems in locoregional deep inspiration breath hold radiotherapy for breast cancer - a multicenter study on the setup accuracy.

Daily image-guided radiotherapy (IGRT) and deep inspiration breath hold (DIBH) technique are recommended for locoregional RT of breast cancer. The optimal workflow for a combination of surface-guided RT (SGRT) with DIBH technique is of current clinical interest. The setup accuracy at three hospitals was evaluated using different SGRT workflows. A total of 150 patients (2269 image pairs) were analyzed in three groups: patient setup with the AlignRT® SGRT system in Tampere (Site 1, n = 50), the Catalyst™ SGRT system in Turku (Site 2, n = 50) and the Catalyst™ SGRT system in Jönköping (Site 3, n = 50). Each site used their routine workflow with SGRT-based setup and IGRT positioning. Residual errors of the bony chest wall, thoracic vertebra (Th 1) and humeral head were evaluated using IGRT images. Systematic residual errors in the cranio-caudal (CC) direction and in pitch were generally larger at Site 2 than those at Sites 1 and 3 (p = 0.01-0.7). With daily IGRT, only a small difference (p = 0.01-0.9) was observed in residual random errors of bony structures in other directions between sites. The introduction of SGRT and the use of daily IGRT lead to small residual errors when combining the best workflow practices from different hospitals. Our multicenter evaluation led to improved workflow by tightening the SGRT tolerances on Site 2 and fixation modification. Because of mainly small random errors, systematic posture errors in the images need to be corrected after posture correction with new setup surfaces. We recommend tight SGRT tolerances, good fixation and correction of systematic errors.

Risk-adapted locoregional radiotherapy strategies based on a prognostic nomogram for de novo metastatic nasopharyngeal carcinoma patients treated with chemoimmunotherapy

To develop a prognostic nomogram for individualized strategies on locoregional radiation therapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) treated with chemoimmunotherapy. Ninety patients with dmNPC treated with chemoimmunotherapy and diagnosed between 2019 and 2022 were included in our study. Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS) to establish a nomogram. With a median follow-up of 17.5 months, the median PFS and OS were 24.9 months and 29.4 months, respectively. Sixty-nine patients and twenty-one patients were included in the LRRT group and without LRRT group, respectively. Multivariate analysis revealed that younger age, lower EBV DNA copy number before treatment, a single metastatic site, more cycles of chemotherapy and immunotherapy were significantly associated with better OS. A prognostic nomogram was constructed incorporating the above 5 independent factors, with a C-index of 0.894. Patients were divided into low- and high-risk cohorts based on nomogram scores. A significant improvement in OS was revealed in the LRRT group compared with the without-LRRT group for patients in the high-risk cohort (HR = 2.46, 95% CI 1.01–6.00, P = 0.049), while the OS was comparable between the two groups in the low-risk cohort. Our study indicates that LRRT may be associated with better prognosis in high-risk patients with dmNPC in the era of immunotherapy.

Loco-regional radiotherapy in de novo metastatic nasopharyngeal carcinoma with chemotherapy and immunotherapy: A real-world retrospective study from two cancer centers.

Immunochemotherapy has become the first-line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco-regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco-regional radiotherapy combined with immunochemotherapy remained unknown. Patients with de novo mNPC who received immunochemotherapy followed by loco-regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow-up was 28 months (range 14-47 months). No one died. One-year, 2-year, and 3-year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy-related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%). Loco-regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy.

Efficacy and safety of the combination of cisplatin plus nab-paclitaxel and nivolumab with radiotherapy after maximal tumor resection in non-metastatic muscle invasive bladder cancer (CNN-BC trial).

TPS723 Background: The therapeutic gold standard for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) preceded by neoadjuvant chemotherapy when appropriate. However, RC is a major surgery procedure with 13% rate of severe complication and a perioperative mortality rate of about 1.5 - 5 %. Trimodal therapy (TMT) is a “bladder sparing” option alternative to RC. TMT consists of complete transurethral bladder tumor resection (TURBT) followed by a combination of systemic chemotherapy and locoregional radiotherapy (RT), with the option of “salvage” cystectomy in case of local treatment failure. Immunotherapy with anti-PD1/PD-L1 monoclonal antibody significantly improves survival of metastatic BC patients, and it seems to potentiate the activity of RT without increased toxicity. Therefore, we investigate the role of a multimodal TMT strategy to increase the disease-free survival (DFS) and avoid or delay RC in non-metastatic MIBC pts. Methods: CNN-BC trial (NCT05203913) is a phase 2, open-label, mono-institutional study evaluating the activity and safety of TMT with cisplatin, nab-paclitaxel and nivolumab as systemic therapy in non-metastatic MIBC pts. Eligible pts should have undergone complete TURBT with diagnosis of T2-T3 N0M0 urothelial carcinoma, and no evidence of lymph nodes or metastatic disease at FDG-PET within 6 weeks from the start of treatments. TMT consists of nivolumab (480 mg IV every 4 weeks for a total of 13 doses), weekly nab-paclitaxel (60mg/m2) plus cisplatin (20mg/m2) administered concurrently with RT (60Gy in 25 fractions over 5 weeks on original bladder tumor, plus a concomitant boost of 50Gy in 25 fractions on whole bladder and pelvic nodes). The primary endpoint is the 1-year DFS rate, defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastases. Secondary endpoints include: the rate of pts who require salvage cystectomy, the rate of locoregional complete response (CR) and of locoregional DFS, median DFS, safety, and quality of life. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05203913 .

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study

BackgroundImmunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice.MethodsPatients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents.ResultsOf the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5–8.2 months) and 17.4 months (95% CI: 15.3–19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79–1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63–1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups.ConclusionsAnti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

The role of locoregional radiotherapy in distant metastatic nasopharyngeal carcinoma cases

Background: Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer primarilytreated with platinum-based chemotherapy. The oligometastasis hypothesis proposed by Hellman andWeichselbaum suggested that controlling the primary tumor through locoregional radiotherapy couldsignificantly improve prolonged disease-free survival. Purpose: To evaluate the effectiveness of combining locoregional radiotherapy with chemotherapy for metastatic NPC. Case series report: The first case involved a 57-year-old male with NPC at T4N3M1 (lungs) with partial response to chemotherapy, who then underwent concurrent chemoradiotherapy. However, his condition deteriorated after completing chemoradiation. The second case featured a 56-year-old male with NPC at T4N3M1 (liver), exhibiting partial response to chemotherapy and remaining at a stable condition after concurrent chemoradiotherapy. Method: Using specific keywords based on clinical questions in the PubMed, Cochrane, EBSCOhost, and Proquest databases. Inclusion criteria, exclusion criteria, and critical appraisal were carried out to find relevant studies. Result: Eleven articles were appraised critically based on the Oxford Centre for Evidence-based Medicine (CEBM) worksheet and include the validity, importance, and applicability in clinical scenarios. Conclusion: Metastatic NPC patients had better overall survival outcomes when treated with locoregional radiotherapy and systemic chemotherapy. Predictive factors influencing survival included oligometastasis, locoregional radiotherapy, chemotherapy response, lactate dehydrogenase, C-reactive protein, EBV DNA, total chemotherapy administration, Karnofsky performance score, number of metastatic lesions, and liver metastases. Platinum-based chemotherapy combined with locoregional radiotherapy could be considered as a management approach for cases of oligometastatic NPC.Keywords: nasopharyngeal carcinoma, chemotherapy, metastasis, overall survival, radiotherapy

Axillary Lymph Node Dissection versus Loco-regional Radiotherapy in Management of the Axilla in Node-Negative Locally Advanced Breast Cancer Post Neoadjuvant Chemotherapy.

To compare the outcomes of axillary lymph node dissection (ALND) and loco-regional axillary radiotherapy (ART) on lymphedema and disease recurrence in locally advanced breast cancer (LABC) cases that have shown a downstaging of their axillary status after neoadjuvant chemotherapy (NACT). Material and Methods: Sixty patients with LABC with an initial cN1-2 disease showed a downstaging of their axillary status to cN0 after NACT. They were randomized into two groups. The first group (the control group) underwent ALND, while the second group (the study group) had a sentinel lymph node biopsy (SLNB) and post-operative ART. Patients with failed SLNB or positive SLNB were excluded. All patients were followed up for loco-regional recurrence and lymphedema for at least one year. Results: No Statistical significance was found between both groups regarding loco-regional recurrence. There was a higher rate of arm lymphedema in the control group. Lymphedema was found in 46.7% of patients who underwent ALND, compared to 13.4% in the study group (patients with SLNB and radiotherapy). Axillary radiation after SNLB has shown no difference regarding axillary recurrence when compared to ALND. However, our results were in favor of radiation concerning lymphedema. With all the ongoing research aiming at reducing axillary surgery, this study could be an initiative for a new strategy in LABC. With all the ongoing research aiming at reducing axillary surgery, this study could be an initiative for a new strategy in LABC for patient who have shown down-staging of their axillary status after NACT. Radiotherapy can show better results in the long term with regards lymphedema.