Hypofractionated Radiotherapy Research Articles

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial

BC2001 showed combining chemotherapy (5-FU+mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). invasive loco-regional control (ILRC); secondary overall survival. Hypoxia affected overall survival (HR=1.30; 95% CI 0.99-1.70; p=0.062): more uncertainty for ILRC (HR=1.29; 95% CI 0.82-2.03; p=0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n=90, HR 1.69; 95% CI 0.99-2.89 p=0.057) but not conventional (n=207, HR 0.70; 95% CI 0.28-1.80, p=0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n=51; HR 14.2; 95% CI 1.7-119; p=0.015) but not conventional (n=24, HR 1.04; 95% CI 0.07-15.5, p=0.978) radiotherapy. Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Cancer Research UK, NIHR, MRC.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE)

BackgroundModerate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series.Materials and methodsWe retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type.ResultsAt the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively.ConclusionReal-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

INITIAL HFRT EXPERIENCE ON TREATING LARGE BRAIN METASTASES LESION: A CASE REPORT

Abstract
 Background: Brain metastases in cancer patients are increasing, due to advances in imaging and systemic treatment. Stereotactic Radiosurgery (SRS) is a high-end radiotherapy technique that is preferred to treat small brain metastases. Hypofractionated Radiotherapy (HFRT) is an alternative technique that demand lower requirements and ideal for treating larger brain metastases. This case report intended to report our institution initial experience using HFRT in limited setting to treat a patient with large brain metastases. 
 Case Presentation: A-43 years old women with previous breast cancer history was admitted with general weakness and severe headache since 2 weeks before admission. A CT scan exam shows multiple metastatic lesions on both parietal lobe, the largest lesion measures ≥ 3cm in diameter with a prominent vasogenic edema that caused lateral ventricle compression and mild midline shift.
 Discussion: SRS is preferred to treat brain metastases due to its efficacy and excellent therapeutic ratio. Unfortunately it has limitation in treating large metastatic lesions. For such lesions, HFRT being a simpler radiation technique can be opted to achieve acceptable local control and low toxicities profile. We use HFRT to treat a patient with large brain metastases lesion using IMRT with 10 x 4Gy fractionation scheme. The evaluation results 6 weeks later shows no viable brain lesion without any cognitive deterioration reported.
 Conclusion: HFRT for large brain metastases treatment is safe and viable to conduct in institution with limited resources. This relatively simpler technique compared to SRS should be considered to achieve acceptable therapeutic ratio with minimal toxicities.

MV CBCT based assessment of setup uncertainties and planning target volume margin in head and neck cancer.

Set-up errors are an undesirable part of the radiation treatment process. The goal of online imaging is to increase treatment accuracy by reducing the set-up errors. This study aimed to determine the daily variation of patient set-up uncertainties and planning target volume (PTV) margins for head and neck cancer patients using pre-treatment verification by mega voltage cone-beam computed tomography (MV-CBCT). This retrospective study was internal record base of head and neck (H&N) cancer patients treated with definitive radiotherapy, adjuvant radiotherapy, and hypo-fractionated radiotherapy at our institution since the implementation of HalcyonTM 2.0 machine (Varian, US). Errors collected from each patient setup were recorded and evaluated for each direction [medio-lateral (ML), supero-inferior (SI), antero-posterior (AP)] discretely. For each patient, the systematic error (∑) and random error (σ) were collected. Clinical target volume (CTV) to planning target volume (PTV) margin was calculated using International Commission on Radiation Units and Measurements (ICRU) 62 ( ), Stroom's (PTV margin = 2∑ + 0.7σ), and Van Herk's (PTV margin = 2.5∑ + 0.7σ) formula. A total of 7900 pre-treatment CBCT scans of 301 patients were analyzed and a total of 23,000 error measurements in the ML, SI, and AP directions were recorded. For all of our H&N cancer patients, the CTV to PTV margin, calculated from the van Herk formula for the head and neck patients was 0.49 mm in the anteroposterior axis. An isometric PTV margin of 5 mm may be considered safe if daily imaging is not being done. In case daily online pretreatment imaging is being utilized, further reduction of PTV margin is possible.

Efficacy and Mechanism of Hypofractionation Radiotherapy Combined with PD-1 Inhibitors in a Model of Head and Neck Melanoma

Head and neck mucosal melanoma is one of the most common types of melanoma in China, but the prognosis is worse than other types, and there is no effective treatment plan to improve patient survival. This study analyzes the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitor in the treatment of head and neck mucosal melanoma, as well as its impact on the tumor immune microenvironment. NPSG mice were used to construct a humanized bilateral lesion tumor model of the humanized immune system. The models were divided into an RT (8 Gy)+anti PD-1 group, an RT (2 GyX4)+anti PD-1 group, an Anti PD-1 group, an RT (8 Gy) group, and a blank group. Differences in efficacy and immune cells in blood, lymph nodes, and tumor tissues were compared between different treatment groups. The treatment effect of RT (8 Gy)+anti PD-1 was better than the other groups with a tumor growth inhibition value (TGI) over 60%. Significant recruitment and activation of CD8+T cells were found in the blood, lymph nodes, and tumor tissues and significantly inhibited the level of PD-1+CD8+T cells in the group of RT (8 Gy)+anti PD-1. This study confirmed the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitors, which can inhibit tumor growth and produce distant effects. The appearance of a distant effect is related to the enhancement in the number and activity of CD8+T cells in the local tumor and peripheral blood and lymph nodes. This study confirms the therapeutic and immune regulatory effect of hypofractionation radiotherapy combined with PD-1 inhibitors.

Optimizing Clinical Implementation of Hypofractionation: Comprehensive Evidence Synthesis and Practical Guidelines for Low- and Middle-Income Settings

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.

Assessment of quality of voice after 3D conformal hypofractionated radical radiotherapy in early-stage glottic cancer: A prospective study

ABSTRACT Purpose: The purpose of this study was to evaluate the short-term outcomes in terms of oncological outcomes, toxicities, and impact of quality of voice on livability of early glottic cancer (EGC) (T1) patients after hypofractionated radiotherapy. Material and Methods: 30 patients of early glottic carcinoma, staged cT1a-T1bN0M0 with Eastern Cooperative Oncology Performance Status (ECOG PS ≤ 2). Exclusion criteria included ECOG PS > 2, T2–T4 disease, and any other head and neck malignancy. Voice Handicap Index-10 (VHI-10) was used to score voice outcomes of patient’s pre- and post-radiation. Results: All the subjects were predominantly smokers (80%) having hoarseness of voice as the most common presenting complaint (76.7%) followed by dry cough (13.3%) and foreign body sensation (10%). On posttreatment response assessment, there has been a significant reduction in VHI-10 scores from pre-radiotherapy (RT) to 6, 12, and 24 weeks post-radiation completion in all three domains (functional, emotional, and physical), as well as total scores, with a significant P value (<0.05) being observed. Conclusion: The use of modest hypofractionated regimen (63 Gy in 28 fractions) in patients of early glottic disease (T1a and T1b) posttreatment completion provides good oncological outcomes with better quality of voice being observed.

Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501).

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p<0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

A single-institution experience of acute toxicities in patients treated with short course hypofractionated radiotherapy in locally advanced rectal cancer.

92 Background: Hypofractionated short course radiation treatment (SCRT) as part of a total neoadjuvant treatment (TNT) approach to treat rectal cancer has increased in popularity since the publication of the RAPIDO trial. However, the literature on SCRT for rectal cancer has not reported significant acute toxicities in the weeks immediately following the completion of treatment. This study examines the acute toxicities in patients treated with hypofractionated radiation therapy as part of their definitive treatment for rectal cancer. Methods: At our institution, we retrospectively analyzed 71 patients with locally advanced rectal cancer treated between 2016-2022 with SCRT (25 Gy in 5 fractions) as part of definitive treatment. Acute toxicity caused by radiation was defined as that occurring from the start of radiation treatment to either 30 days post radiation completion, the start of chemotherapy, or date of surgery, whichever occurred first. Acute neuropathic lumbosacral (LSN) pain was defined as bilateral radiating pain down the lower extremities. Matched patients without reported LSN pain were identified and matched on N stage, location of tumor, and treatment position. Organs at risk were contoured on the CT planning scan and dosimetric analysis was conducted on the patient’s treatment plan. Results: In 71 patients treated with SCRT, we identified diarrhea (n=34, 47.9%), rectal pain (n=15, 21.1%), rectal urgency (n=15, 21.1%) nausea (n=14, 19.7%), and rectal bleeding (n=12, 16.9%) as frequent acute toxicities in the setting of SCRT. For patients with rectal pain, 31.2% required steroids. We also identified an acute toxicity of LSN pain in 10 patients (14.1%). Patients rated this LSN pain between moderate and severe; median time to LSN pain was 2 days (range 1-6 days). For LSN pain, management was conservative for 3 (30%) patients and symptoms self-resolved. The other 7 patients required ibuprofen and acetaminophen treatment; 2 of these patients had persistent symptoms and one was treated with topical hydrocortisone and gabapentin and the other with a burst of methylprednisolone. Dosimetric analysis of the lumbosacral nerve plexus area did not detect a statistically significant difference in dose parameters between symptomatic and asymptomatic patients. Conclusions: We have identified acute toxicities in patients treated with short course hypofractionated radiation, including diarrhea, rectal pain requiring steroid treatment, and previously underappreciated neuropathic lumbosacral pain. Toxicities mainly occurred within one week of treatment and resolved. Further analysis will seek to identify predictive factors of these acute toxicities and to determine whether there is a correlation between these observed acute toxicities and long-term outcomes.

Hypofractionated Radiotherapy in Gynecologic Malignancies-A Peek into the Upcoming Evidence.

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era

BackgroundRadiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed.MethodsWe retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed.ResultsA total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3–5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2–27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported.ConclusionThese data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Hypofractionated Radiotherapy for Hematologic Malignancies during the COVID-19 Pandemic and Beyond.

Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6-17 fractions/2.67-5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort and 100, 87 (95% CI: 56.4-96.5%), and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9-90.5%) and 100, 66.1 (95% CI: 36.4-84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. HFRT in HM provides excellent local control to be validated in a larger prospective study.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy

BackgroundThe role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. MethodsPatients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. ResultsFifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19–78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10−20 Gy), 27 Gy (range, 18−33 Gy) and 25 Gy (range, 25−30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. ConclusionOur findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

A Comparative Analysis of Hypofractionated and Conventional Radiotherapy for Breast Cancer Patients: A Retrospective Cohort Study

Breast cancer presents a substantial health challenge in Africa and marked by a continuous rise in its incidence and prevalence. The complexities of managing breast cancer on the continent are exacerbated by limited access to healthcare resources and high rates of late-stage disease at initial diagnosis. Recent studies comparing hypofractionated radiotherapy (HFRT), considered cost-effective and non-inferior to conventional fractionated radiotherapy (CFRT), have shown no significant differences in outcomes. This underscores the potential significance of HFRT in breast cancer treatment. Despite encouraging findings from researchers in developing countries, there is a noticeable lack of data on HFRT outcomes, particularly in Sub-Saharan Africa. This retrospective study analyzed individuals diagnosed with early, locally advanced or oligometastatic cancer, and who underwent treatment between January 2010 and December 2020 at Inkosi Albert Luthuli Central Hospital in the KwaZulu Natal Province of South Africa. Relevant clinical treatment details and follow-up information were retrieved from the patients' medical electronic records. This retrospective study included 645 breast cancer patients, categorized into early (37.7%), locally advanced (59.9%), and oligometastatic (2.4%) stages. Treatment modalities included surgery (100%), chemotherapy (77.8%), endocrine therapy (38.8%), and targeted therapy (4.8%). All patients received radiotherapy, with a predominant utilization of HFRT (83.7%) over CFRT (16.3%). Notably, there was no statistically significant difference (p=0.91) observed in survival probability between patients who received HFRT and CFRT. The findings of this study suggest that, in a low-income setting, HFRT does not exhibit a significant variance in survival outcomes compared to CFRT for breast cancer patients. However, to validate this conclusion, additional large-scale randomized clinical trials are imperative.

Long-term treatment results of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients: A retrospective study from rural cancer center of Maharashtra, India.

This study aims to evaluate the long-term treatment outcome of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients. A total of 140 postmastectomy breast cancer patients were included in this retrospective study, who were treated from 2012 to 2014 with chemotherapy and various fractionation radiotherapy schedules. Radiotherapy treatment records for study group-I received radiotherapy 4256 cGy in 16 fractions over 3½ weeks, group-II patients received 4005 cGy in 15 fractions over 3 weeks, and conventional radiotherapy group-III received 5000 cGy in 25 fractions over 5 weeks. The median follow-up of patients from all groups was 60 months (range 9 to 111 months). There were 39 cases with disease failure, 13 (26%) in group I (42.56 Gy), 16 (40%) in group II (40.05 Gy), and 10 (20%) in group III (50 Gy). There were 4 locoregional recurrences (LRRs), two isolated, and 11 distant failures in group I, 3 LRRs (1 isolated LRR) and 15 distant failures in group II, and only one LRR and 9 distant failures in group III. The disease-free survival (DFS) were 74%, 60%, and 80%, respectively, in groups I, II, and III (P =0.044). The long-term results of this study show that hypofractionation radiotherapy in postmastectomy cases is well tolerated and acute and late side effects are also comparable to conventional fractionation. In our study, locoregional and distant failure seems slightly higher with hypofractionation schedules than in other studies, highlighting the need for more studies with long-term follow-up in postmastectomy patients.

Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.

Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers.

The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

Radiobiological evaluation of hypo-fractionated breast cancer radiotherapy regimens in comparison with conventional approaches

Abstract Purpose: This study compares tumor control probability (TCP) and normal tissue complication probability (NTCP) across different hypo-fractionated (HypoRT) and conventional breast radiotherapy regimens using radiobiological models. Materials and methods: Computed tomography data from 30 patients with left breast-conserving surgery were used to evaluate three HypoRT regimens (39 Gy and 41·6 Gy in 13 fractions, and 40 Gy in 15 fractions) and a conventional regimen (50 Gy in 25 fractions). Dose-volume histograms (DVHs) were extracted for radiobiological calculations using Equivalent Uniform Dose (EUD) and Poisson models for TCP, and EUD and LKB (Lyman-Kutcher-Burman) models for NTCP. Results: Conventional treatment achieved significantly higher TCP (95%) than all HypoRT regimens (p &lt; 0·001), with no significant differences between HypoRT regimens (p &gt; 0·05. The 39 Gy/13 fraction regimen showed the lowest lung NTCP (p &lt; 0·05). HypoRT regimens had significantly lower NTCP for the lungs and heart compared to the conventional regimen (p &lt; 0·01). TCP and NTCP values from Poisson and LKB models were higher than those from the EUD model (p &lt; 0·01). Conclusion: HypoRT regimens reduced NTCP, with the lowest values in the regime of 39 Gy/13 fractions regimen, though the conventional regimen had higher TCP.

A comparative study of conventional and hypofractionated radiotherapy in postmastectomy breast cancer patients

A comparative study of conventional and hypofractionated radiotherapy in postmastectomy breast cancer patients

Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.