Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities.

BACKGROUND: The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. METHODS: The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan-Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. RESULTS: During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1-2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1-2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. CONCLUSIONS: 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Carbon-ion radiotherapy for clear cell odontogenic carcinomas.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignant tumor. The standard treatment for CCOC is surgical resection and adjuvant radiotherapy (RT). Radiotherapy is generally considered in inoperable cases. However, there are no reports on definitive RT for CCOC, and the role of RT in patients with inoperable CCOC remains unknown. Therefore, in this report, we present two cases of carbon-ion (C-ion) RT for CCOC. CASE PRESENTATION: In case 1, a 73-year-old man with mandibular CCOC presented with recurrence in the inferior temporal fossa after two tumor resections. The tumor was considered inoperable, and C-ion RT (57.6 Gy in 16 fractions) was administered. The tumor remained controlled even after 20 months of C-ion RT; however, the patient died of other causes. In case 2, a 34-year-old man with maxillary CCOC presented with recurrence in the left sinonasal region after two tumor resections. The tumor was considered inoperable, and C-ion RT (64 Gy in 16 fractions) was administered. However, recurrence was observed in the irradiated field 19 months after the treatment. Subsequently, C-ion RT (64 Gy in 16 fractions) was repeated for the recurrent tumors. Seven years and 6 months after the initial irradiation, the tumor remains controlled, and the patient is alive without any unexpected serious adverse events. CONCLUSION: C-ion RT may be an effective treatment option for patients with inoperable CCOC.

Long-term Outcome After Helical Tomotherapy Following Breast Conserving Surgery for Ductal Carcinoma In Situ.

Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.

Oral Cavity Squamous Cell Carcinoma: Impact of Clear Margin Distance on Locoregional Control in Patients Undergoing Postoperative Radiotherapy.

INTRODUCTION: Postoperative radiotherapy can improve locoregional control (LC) in oral cavity squamous cell carcinoma (OCSCC) patients with positive resection margins. The present study aimed to evaluate the impact of surgical margin size on LC in this patient population. METHODS: This retrospective study involved 162 patients with OCSCC who underwent postoperative radiotherapy between 2000 and 2020 at the Department of Radiation Oncology, University Hospital Heidelberg and the German Cancer Research Center. The study aimed to determine the impact of different resection margins on LC, as well as overall survival (OS), progression-free survival (PFS), and treatment-related toxicity (CTCAE 4.03). RESULTS: Seventy-seven patients (47.5%) had involved (<1 mm) margins, 22 patients (13.6%) close (≤5 mm) margins, and 63 patients (38.9%) clear (>5 mm) margins. A surgical margin ≤ 5 mm was a significant predictor for worse LC (HR 2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2, 0.7, 2.0). CONCLUSION: Patients who have narrow resection margins (1-5 mm) experience poor local control and should receive postoperative radiotherapy. It is necessary to conduct further prospective studies to determine whether a narrower margin window could be achieved to better determine the appropriate indication for adjuvant radiotherapy.

Stereotactic Body Radiotherapy Reirradiation Is Safe in Patients With Lung Cancer With In-Field Enlarged Tumor Recurrence.

Introduction: Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Materials and Methods: Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. Results: The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 standard fractionation). For SABR, the median biologically effective dose at an α/ß ratio of 10 (BED10) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED10 ≥ 50 Gy developed no local recurrence (P = .044). Discussion: In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED10 ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.

Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Long-term outcomes after particle radiation therapy in patients with nasopharyngeal adenoid cystic carcinoma.

BACKGROUND: Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC. METHODS AND MATERIALS: Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method. RESULTS: The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed. CONCLUSION: Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.

Proton therapy re-irradiation outcomes and genomic landscape of patients with recurrent head and neck cancer.

INTRODUCTION: Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is challenging. We describe clinical outcomes and toxicity of proton therapy (PT) for recurrent HNC, and report genomic alterations associated with patterns of failure. MATERIALS & METHODS: We performed a retrospective analysis of rHNC patients treated with PT. Outcomes were estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA) were performed to assess multiple patient factors. Next-generation sequencing and genomic analyses were performed on available samples. RESULTS: Eighty-nine patients treated with PBS-PT for rHNC with a median follow-up of 12 mo (0-71 mo) were included. The 1- and 2-y local control (LC) rates were 80.8 % (95 % CI: 70.8-90.8) and 66.2 % (95 % CI: 50.7-81.7), and 1- and 2-y distant metastasis-free survival (DMFS) were 41.0 % (95 % CI: 30.0-52.0) and 26.3 % (95 % CI: 15.7-36.9). The median overall survival (OS) was 13 mo (95 % CI: 9.3-16.7). On UVA and MVA, smaller gross tumor volume (GTV) was associated with improved OS (HR 1.002, P = 0.004), DMFS (HR 1.002, P = 0.004), and PFS (HR 1.002, P = 0.014). There were 35 late Gr3 + toxicity events (30.3 %). Patients with higher candidate gene-specific mutation burden (genes with [OR] > 2, P < 0.05) had inferior PFS. TP53, NOTCH4, and ARID1B mutations were associated with inferior DMFS (OR > 2, P < 0.05). CONCLUSIONS: PBS-PT is effective at achieving LC for rHNC with favorable toxicity. Distant metastases are common, and associated with TP53, NOTCH4, and ARID1B mutations. Inclusion of genomic alterations in the clinical decision process may be warranted.

125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy.

OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.

HyperArcTM volumetric modulated arc therapy for hypopharyngeal cancer with solitary recurrence in the cervical vertebra: A case report and literature review.

RATIONALE: It is difficult to reirradiate head and neck cancers because of the toxicity from previous radiation dose delivery. Conventional volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy often have poor target coverage. The new HyperArcTM VMAT (HA-VMAT) planning approach reportedly has better target coverage, higher conformity, and can spare normal organs compared to conventional VMAT; however, research on recurrent head and neck cancers is limited. Here, we report the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence in the first cervical vertebra (C1). PATIENT CONCERNS: A 52-year-old Asian male was diagnosed with a hypopharyngeal cancer. The patient received concurrent chemoradiotherapy with a radiation dose of 70 Gy in 33 fractions and achieved complete clinical response. Two years later, solitary recurrence was observed in the C1 vertebra. DIAGNOSES: Solitary recurrence in the C1 vertebra. INTERVENTIONS: Owing to concerns regarding the toxicity to adjacent organs, we decided to use HA-VMAT to achieve better tumor coverage and critical organ sparing. OUTCOMES: Tumor regression was observed on the imaging. At 9 months follow-up, the patient was disease-free and had no late toxicities. LESSONS: This is the first report regarding the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence over the C1 vertebra. HA-VMAT achieves highly conformal dose distribution and excellent sparing of critical organs. There was a favorable initial clinical response with no toxicity. Long-term follow-up is essential in such cases.

Is Perioperative Radiotherapy Effective in Preventing Local Recurrence in Myxofibrosarcoma?

Background: Myxofibrosarcoma (MFS) is a rare type of soft tissue sarcoma that is locally aggressive and has a high risk of recurrence. The effectiveness of perioperative radiotherapy (RT) in preventing local recurrence (LR) of MFS remains uncertain. This retrospective study aimed to evaluate the impact of perioperative radiotherapy on local recurrence in patients with MFS. Methods: A total of 75 patients diagnosed with MFS and treated at a single institution were included in the study. Patient data, including demographics, tumor characteristics, and treatment variables, were collected from electronic medical records. The primary endpoint was the occurrence of local recurrence. Results: Among the patients, 25/75 (33.3%) received radiation therapy, while 50/75 (66.7%) did not. Local recurrence in the radiated group was 28% (7/25) compared to 36% (18/50) in the non-irradiated group (p = 0.20). The LR rate trended higher in patients who received RT postoperatively (adjuvant) (6/12, 50%) than preoperatively (neoadjuvant) (1/13, 7.6%) (p = 0.124). Of the 54 patients with negative margins, the local recurrence rate was lower in the radiated group (1/12, 8.33) than the non-irradiated group (9/36, 25%) (p = 0.034). A subgroup analysis based on tumor grade did not reveal any significant differences in recurrence rates between the radiated and non-irradiated groups. Furthermore, there was no significant difference in recurrence rates between the irradiated and non-irradiated groups at the one-year (p = 0.32), two-year (p = 0.24), and five-year (p = 0.32) follow-up marks. Conclusion: Although radiotherapy demonstrated a trend toward reduction in recurrence rates in patients with MFS in this study, the observed difference did not reach statistical significance. Neoadjuvant radiation appears to be more effective than adjuvant radiation. However, there was a significant reduction in recurrence in patients with negative margins who received radiation demonstrating that effective surgical resection continues to be the most important intervention in patients with myxofibrosarcoma. Level of Evidence: III.

Survival and toxicity after breast-conserving surgery and external beam reirradiation for localized ipsilateral breast tumour recurrence: A population-based study.

PURPOSE: Breast-conserving surgery followed by reirradiation for a localized ipsilateral breast tumour relapse may increase the radiation dose delivered to the heart and result in a greater risk of cardiac adverse events. This study aimed to compare the incidence of cardiac mortality in patients treated for a localized ipsilateral breast tumour relapse, either with breast-conserving surgery followed by reirradiation or with total mastectomy between 2000 and 2020. MATERIALS AND METHODS: All patients treated for a primary non-metastatic breast cancer with breast-conserving surgery and adjuvant radiotherapy were identified in the Surveillance, Epidemiology, and End Results (SEER) program database, and those who subsequently experienced a localized ipsilateral breast tumour relapse treated with breast-conserving surgery and reirradiation ("BCS+ReRT" group, n=239) or with total mastectomy ("TM" group, n=3127) were included. The primary objective was to compare the cardiac mortality rate between the patients who underwent breast-conserving surgery followed by reirradiation and total mastectomy. Secondary endpoints were overall survival and cancer specific survival. RESULTS: Cardiac mortality was significantly higher in patients treated with breast-conserving surgery followed by reirradiation (hazard ratio [HR]: 2.40, 95% confidence interval [95% CI]: 1.19-4.86, P=0.006) in univariate analysis; non-statistically significant differences were observed after adjusting for age, laterality and chemotherapy on multivariate analysis (HR: 1.96, 95% CI: 0.96-3.94, P=0.067), age being the only confounding factor. A non-statistically significant difference towards lower overall survival was observed in patients who had breast-conserving surgery followed by reirradiation compared with those who underwent total mastectomy (HR: 1.37, 95% CI: 0.98-1.90, P=0.066), and no differences were observed in terms of cancer specific survival (HR: 1.01, 95% CI: 0.56-1.82, P=0.965). CONCLUSION: In this study, the incidence of cardiac mortality was low, and breast-conserving surgery followed by reirradiation did not independently increased the risk of cardiac mortality for a localized ipsilateral breast tumour relapse.

Dose-response relationship between volume base dose and tumor local control in definitive radiotherapy for vaginal cancer.

OBJECTIVE: This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina. MATERIALS AND METHODS: We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion. RESULTS: A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 GyEQD2,10 (95% CI: 75.3-96.6 GyEQD2,10). CONCLUSIONS: A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.

Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience.

PURPOSE: GammaTile® (GT) is a brachytherapy platform that received Federal Drug Administration (FDA) approval as brain tumor therapy in late 2018. Here, we reviewed our institutional experience with GT as treatment for recurrent glioblastomas and characterized dosimetric parameter and associated clinical outcome. METHODS AND MATERIALS: A total of 20 consecutive patients with 21 (n = 21) diagnosis of recurrent glioblastoma underwent resection followed by intraoperative GT implant between 01/2019 and 12/2020. Data on gross tumor volume (GTV), number of GT units implanted, dose coverage for the high-risk clinical target volume (HR-CTV), measured by D90 or dose received by 90% of the HR-CTV, dose to organs at risk, and six months local control were collected. RESULTS: The median D90 to HR-CTV was 56.0 Gy (31.7-98.7 Gy). The brainstem, optic chiasm, ipsilateral optic nerve, and ipsilateral hippocampus median Dmax were 11.2, 5.4, 6.4, and 10.0 Gy, respectively. None of the patients in this study cohort suffered from radiation necrosis or adverse events attributable to the GT. Correlation was found between pre-op GTV, the volume of the resection cavity, and the number of GT units implanted. Of the resection cavities, 7/21 (33%) of the cavity experienced shrinkage, 3/21 (14%) remained stable, and 11/21 (52%) of the cavities expanded on the 3-months post-resection/GT implant MRIs. D90 to HR-CTV was found to be associated with local recurrence at 6-month post GT implant, suggesting a dose response relationship (p = 0.026). The median local recurrence-free survival was 366.5 days (64-1,098 days), and a trend towards improved local recurrence-free survival was seen in patients with D90 to HR-CTV ≥ 56 Gy (p = 0.048). CONCLUSIONS: Our pilot, institutional experience provides clinical outcome, dosimetric considerations, and offer technical guidance in the clinical implementation of GT brachytherapy.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. METHODS: The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. RESULTS: Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. CONCLUSIONS: The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. ADVANCES IN KNOWLEDGE: Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Interventional radiotherapy (brachytherapy) for re-irradiation of recurrent head and neck malignancies: oncologic outcomes and morbidity.

Objective: Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity. Methods: This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT. Results: Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%. Conclusions: The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.