Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

Clinical outcomes analysis of image-guided brachytherapy as definitive treatment for inoperable endometrial cancer.

OBJECTIVES: This study evaluates the efficacy and toxicity of image-guided brachytherapy combined with or without external beam radiotherapy (IGBT ± EBRT) as definitive treatment for patients with inoperable endometrial cancer (IOEC), in addition to establishing a risk classification to predict prognosis. METHODS: Fifty-one IOEC patients who underwent IGBT ± EBRT at Peking Union Medical College Hospital from January 2012 to December 2021 were retrospectively analyzed, of which 42 patients (82.4%) were treated with IGBT + EBRT and 9 patients (17.6%) with IGBT alone. Establishing risk classification based on FIGO 2009 staging and biopsy pathology, stage III/IV, non-endometrioid, or Grade 3 endometrioid cancer were included in the high-risk group (n = 25), and stage I/II with Grade 1-2 endometrioid cancer was included in the low-risk group (n = 26). RESULTS: The median follow-up time was 58.0 months (IQR, 37.0-69.0). Clinical complete remission (CR) was achieved in 92.2% of patients after radiotherapy (n = 47). The cumulative incidences of locoregional and distant failure were 19.6% (n = 10) and 7.8% (n = 4), respectively. A total of 20 patients died (39.2%), including 10 cancer-related deaths (19.6%) and 10 comorbidity-related deaths (19.6%). The 5-year locoregional control (LRC), time to progression (TTP), overall survival (OS), and cancer-specific survival (CSS) were 76.9%, 71.2%, 59.4%, and 77.0%, respectively. No Grade 3 or above acute or late toxicities were reported. In univariate analysis, LRC, TTP, and CSS were significantly higher in the low-risk group than in the high-risk group (P < 0.05). After adjusting for age, number of comorbidities, radiotherapy modality, and chemotherapy, the low-risk group was still significantly better than the high-risk group in terms of LRC (HR = 6.10, 95% CI: 1.18-31.45, P = 0.031), TTP (HR = 8.07, 95% CI: 1.64-39.68, P = 0.010) and CSS (HR = 6.29, 95% CI: 1.19-33.10, P = 0.030). CONCLUSIONS: IGBT ± EBRT is safe and effective as definitive treatment for IOEC patients, achieving satisfactory locoregional control, favorable survival outcomes, and low toxicity. Risk classification based on FIGO 2009 staging and biopsy pathology is an independent prognostic factor for LRC, TTP, and CSS.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

OBJECTIVE: Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). METHODS: Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. RESULTS: Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. CONCLUSIONS: Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

Definitive chemo-radiotherapy in cervical oesophageal cancer: a comprehensive review of literature.

Background and Objectives: Despite decades of experience with definitive chemo-radiotherapy (CRT) in cervical oesophageal cancer (CEC), the loco-regional control and survival outcomes are dismal. This review evaluated the outcomes of various treatment strategies being commonly utilized. Materials and methods: A literature review was conducted to identify relevant articles on CEC published from years 2000-2023 addressing the predefined key questions. These questions focussed on the comparative outcomes of various primary treatment approaches (surgery, CRT, or trimodality treatment) and the radiation dose schedules, volumes, and techniques. Results: CRT is the standard approach for treatment for CEC so far. The potential role of surgery and trimodality approach in settings of evolving surgical approaches needs to be validated. The high dose schedules that are preferentially practiced in CEC have not shown any benefit in improving the disease outcomes over the standard dose schedule of 50.4 Gy. The target volume delineation practice of elective nodal irradiation (ENI) does not have a proven benefit over the involved field irradiation (IFI). The limited evidence on radiation techniques suggests that intensity-modulated radiotherapy/volumetric-modulated arc therapy (IMRT/VMAT) techniques can improve toxicity profile over three-dimensional conformal radiotherapy (3DCRT), but no advantage proven in disease outcomes so far. Conclusion: This review will guide clinicians in decision-making for the management of this relatively rare entity and the directions for future research in these areas. Future large-scale multicentre prospective studies are needed for validating and standardizing our current practices and exploring potential options to improve the outcomes.

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT).

BACKGROUND: Ultra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT-utilizing potentially fewer treatments-is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment. METHODS/DESIGN: A total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10-14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7-10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score. DISCUSSION: FORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04984343 . Date of registration: July 30, 2021. PROTOCOL VERSION: 4.0, Nov 8, 2022.

Radiotherapy alone for pediatric patients with craniopharyngioma.

PURPOSE: Radiotherapy alone, without tumor-directed surgery, may be appropriate for selected patients with craniopharyngioma reducing the risks associated with neurosurgery. Understanding outcomes for patients with craniopharyngioma treated with radiotherapy alone will further refine patient selection and treatment options. METHODS: Since 2002, 13 children, adolescents and young adults, with craniopharyngioma were treated with radiotherapy alone and followed for disease control and functional outcomes at a single institution. The median age at treatment was 13 years (range, 3-21 years). All patients received 54 Gy/54 Gy(RBE) in 30 fractions. Five patients were treated with intensity-modulated photon therapy, four with passively scattered proton therapy, and four with intensity-modulated proton therapy. RESULTS: With a median follow-up of 5 years (range 3 months-14 years), all patients were alive. One experienced tumor progression 8.5 years after treatment. No significant changes in vision, hearing or neurologic function attributed to radiotherapy. Hormone deficiencies and body mass index were within the expected range at baseline and 5 years after treatment. There was no evidence of cognitive decline based on assessment of IQ, memory and attention. Unexpected complications included single cases of out-of-field malignancy, white matter changes, large vessel narrowing, and pontine capillary telangiectasia. Six patients had sphenoid bone abnormalities on follow-up imaging attributed to radiotherapy. CONCLUSION: Radiotherapy alone is an important treatment option to consider when radical resection is contraindicated, or surgical intervention is not required to alleviate symptoms. Disease control and functional outcomes are excellent after radiation therapy alone in appropriately selected patients.

A hesitated approach: primary radiotherapy for keloids-a case series.

PURPOSE: To assess the efficacy and toxicity of hypofractionated radiotherapy (RT) alone in treatment-resistant symptomatic keloids. METHODS: Six patients with a total of 13 inoperable large keloid lesions and no response to previous treatments were admitted to our department between 2017 and 2019. All patients were examined for detailed wound localization, size, contour, and color assessment, and for objective and subjective symptoms. Response to treatment was graded as "complete remission" in case of full symptomatic relief and >75% decrease in lesion size, as "partial remission" in case of partial symptomatic relief and 25-75% decrease in lesion size, and as "stable disease" in case of no symptomatic relief or <25% decrease in lesion size. Patients were followed up monthly for the first 3 months and every 3 months thereafter by physical examination. RESULTS: A total dose of 37.5 Gy external RT in five fractions was prescribed by 6­MeV electrons in 4 patients and 6­MV photons in 2 patients. Complete response was obtained in all patients at the 6­month control. All patients were satisfied with cosmetic results at their last control. Grade 2 dermatitis developed in all patients during the second week of RT but resolved completely in all after 6 months following the end of RT. CONCLUSION: In keloids that are unresponsive to standard treatment, hypofractionated RT using a total dose of 37.5 Gy in five fractions is feasible.

Magnetic resonance imaging-based validation of the 2018 FIGO staging system in patients treated with definitive radiotherapy for locally advanced cervix cancer.

OBJECTIVE: To validate the revised 2018 International Federation of Gynecologic and Obstetrics (FIGO) staging system in patients who underwent diagnostic magnetic resonance imaging (MRI) and radiotherapy (RT) for locally advanced cervix cancer. METHODS: We analyzed 677 patients who were diagnosed with pelvic MRI and treated with definitive (chemo-)RT for locally advanced cervix cancer (stage IB2/IIA2-IVA or N+) between 1992 and 2018. Patients were classified according to 2009 and 2018 FIGO staging, and survival outcomes were compared. We developed a nomogram to improve prediction of progression-free survival (PFS). RESULTS: Pelvic and paraaortic lymph nodes were positive in 331 (48.9%) and 78 (11.5%) patients, respectively. At a median follow-up of 77.9 months, the 5-year PFS was 83.5%, 65.2%, 71.0%, 60.6%, 37.6% and 38.9% for IB, IIA, IIB, IIIA, IIIB and IVA according to FIGO 2009 and 88.9%, 60.0%, 73.8%, 66.7%, 36.3%, 68.9%, 43.6%, and 38.9% for IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA according to FIGO 2018, respectively. Survival of stage IIIC cervix cancer depended on the local extent of the tumor: the 5-year PFS of T1, T2, and T3 stages were 80.3%, 73.9%, and 45.5% for IIIC1 and 100%, 44.9%, and 23.4% for IIIC2. Histology, tumor size, node metastasis, FIGO 2009, and treatment modality were independent prognostic factors in the Cox regression analysis, and the nomogram incorporating these factors outperformed FIGO 2009 and FIGO 2018 (AUC 0.718 vs. 0.616 vs. 0.594). CONCLUSIONS: FIGO 2018 revision was associated with heterogenous outcomes among stage III cervix cancer patients. Our nomogram can assist the FIGO system in predicting PFS after definitive RT.

The role of radiation therapy in the management of cutaneous malignancies. Part I: Diagnostic modalities and applications.

Radiation therapy offers distinct advantages over other currently available treatments for cutaneous malignancies in certain circumstances. Dermatologists and dermatologic surgeons should be familiar with the available radiation therapy techniques as well as their value and potential limitations in a variety of clinical scenarios. The first article in this 2-part continuing medical education series highlights the mechanisms, modalities, and applications of the most commonly used radiotherapy treatments as they relate to cutaneous oncology. We review the current indications for the use of radiation in the treatment of various cutaneous malignancies, the techniques commonly employed in modern radiotherapy, and the associated complications.

Mutation profiling of uterine cervical cancer patients treated with definitive radiotherapy.

OBJECTIVE: To elucidate tumor mutation profiles associated with outcomes of uterine cervical cancer (UCC) patients treated with definitive radiotherapy. METHODS: Ninety-eight patients with newly diagnosed and pathologically confirmed UCC (82 squamous cell carcinomas, 12 adenocarcinomas, and four adenosquamous carcinomas) who were treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Genetic mutations were identified and analyzed for correlations with clinical outcome. RESULTS: Recurrent mutations were observed in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes (i.e., FGFR1-4) was almost as high (24.5%) as that in PIK3CA and ARID1A, both of which are well-studied drivers of UCC. Fifty-five percent (21 of 38) of the identified FGFR mutations were located in the FGFR protein tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%, respectively; P = 0.010). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS (P = 0.005), independent of clinicopathological variables. CONCLUSIONS: FGFR mutations are associated with worse PFS in UCC patients treated with definitive radiotherapy. These results warrant further validation in prospective studies.

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

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

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review.

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation. METHODS: A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour volume" and "prognostic factors". RESULTS: After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results. CONCLUSION: The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Image-guided, intensity-modulated radiation therapy in definitive radiotherapy for 1433 patients with cervical cancer.

OBJECTIVE: Image guidance should be used for patients with cervical cancer treated with definitive intensity-modulated radiation therapy (IMRT). In this study, we provided a pattern of image guidance and verified it in a large population. METHODS: We retrospectively analyzed patients with stages IB1-IVA cervical cancer treated with IMRT combined with high-dose brachytherapy and concurrent chemotherapy in our institute from January 2005 to December 2015. A dose of 50.4 Gy in 28 fractions was prescribed to the planning target volume with fixed-field IMRT, volumetric modulated arc therapy, or helical tomotherapy. Daily megavoltage computed tomography (CT) or weekly cone-beam CT (CBCT)/CT-on-rail were used for image guidance. Considering tumor regression during treatment, a second CT simulation and IMRT planning after 20 fractions of IMRT was performed. RESULTS: A total of 1433 patients were included in this study. Four hundred thirteen patients (28.8%) had regional lymph node metastases. A total of 1261 patients (88.0%) received concurrent chemotherapy. The median follow-up was 32.2 months (range, 1.9-124.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates were 83.0%, 75.0%, and 87.4%, respectively. The 3-year DFS rates for patients with stages IB1, IB2, IIA, IIB, IIIA, IIIB, and IVA disease were 90.2%, 87.6%, 84.0%, 76.7%, 61.6%, 59.8%, and 25.9%. The incidence rates of grade 3 or greater chronic gastrointestinal and genitourinary toxicities were 2.3% and 1.3%. CONCLUSION: This pattern of image guidance was rational for patients with cervical cancer treated with IMRT. The survival rates were high, and the toxicities were acceptable.

Prognostic impact of nodal relapse in definitive prostate-only irradiation.

BACKGROUND: Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI. MATERIALS AND METHODS: Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed. RESULTS: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome. CONCLUSIONS: Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

[18F]Fluorodeoxyglucose uptake by positron emission tomography predicts outcomes for oropharyngeal and hypopharyngeal cancer treated with definitive radiotherapy.

This study evaluated the prognostic significance of the maximum standardized uptake value of the primary site (pSUVmax) in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of patients with oropharyngeal or hypopharyngeal cancer who were treated using definitive radiotherapy. The study included 86 patients who were primarily treated with radiotherapy for oropharyngeal or hypopharyngeal cancer. Sixty-nine patients underwent concurrent chemotherapy. The associations between pre-treatment pSUVmax and treatment outcomes were evaluated. The most appropriate pSUVmax cut-off value for predicting disease-free survival (DFS) and local control (LC) was selected using receiver operating characteristic (ROC) curves. The median follow-up time for surviving patients was 60 months, while the median survival time in the entire patient cohort was 55 months. A pSUVmax cut-off value of 9.0 showed the best discriminative performance. Five-year OS and DFS rates were 65.9% and 60.0%, respectively. In univariate analyses, pSUVmax (p = 0.009), T-stage (p = 0.001), N-stage (p = 0.039), and clinical stage (p = 0.017) were identified as significant prognostic predictors for DFS. The multivariate analysis did not identify any statistically significant factors, but the association between pSUVmax and DFS was borderline significant (p = 0.055). Interestingly, pSUVmax was predictive of local controllability in T1-T2 disease (p = 0.024), but there was no significant association for T3-T4 disease (p = 0.735). In this study, pSUVmax was predictive of DFS and LC in patients with oropharyngeal or hypopharyngeal cancer that was treated with definitive radiotherapy. pSUVmax was strongly associated with LC in T1-T2 disease.

Primary definitive radiotherapy with or without chemotherapy for squamous cell carcinoma of the temporal bone.

We aimed to evaluate the impact of concurrent chemoradiotherapy (CCRT) on the survival of patients with squamous cell carcinoma of the temporal bone. We retrospectively analyzed the data of 13 consecutive patients who were treated by definitive radiation therapy (RT) or CCRT as the initial treatment between 1999 and 2012. There were 5 patients with stage II disease, 5 with stage III, and 3 with stage IV, as classified according to the University of Pittsburgh system. Among these, 2, 4, and 3 patients, respectively, were treated by CCRT; whereas the remaining (3 patients with stage II and 1 with stage III) were treated by RT alone. Median follow-up duration was 39 months (12-106 months) in all cases, and 61.5 months (17-70 months) in censored cases. The 5-year overall survival (OS) rates were 51 % in all patients, and 40, 100, and 0 % in patients with stage II, stage III, and stage IV disease, respectively. In patients with stage II and III disease, the 5-year OS rates were 80 % in the CCRT group and 50 % in the RT-alone group. We found better prognosis in patients with stage II and III disease who were treated by CCRT. Only 2 patients treated by CCRT experienced adverse events more than grade 3, which were neutropenia and dermatitis. There was no late adverse event of bony necrosis. Our study results indicate that CCRT is safe and very effective as a first-line treatment for stage II and III squamous cell carcinoma of the temporal bone.

Reduced-dose radiotherapy for stage IE gastric mucosa-associated lymphoid tissue lymphoma: a multi-institutional prospective study (KROG 16-18).

PURPOSE: Definitive radiotherapy (RT) of 30 Gy or higher is commonly recommended to treat Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue (MALT) lymphoma with an excellent disease control rate. However, the efficacy of reduced-dose RT has not yet been evaluated in a prospective cohort study. This multi-institutional study aimed to determine the role of reduced-dose RT in the treatment of stage IE gastric MALT lymphoma. METHODS: Between March 2017 and June 2022, 62 patients with histologically confirmed stage IE gastric MALT lymphoma without evidence of H. pylori infection were enrolled. The patients were treated with reduced-dose RT at a total dose of 24-25.5 Gy to the entire stomach. The response to therapy was evaluated by endoscopy with a biopsy of suspicious lesions if necessary. The primary endpoints were 6-month complete remission (CR) and local failure-free survival (LFFS). RESULTS: Among 62 patients, 32 (51.6%) were previously treated for H. pylori eradication. Radiotherapy was delivered using 3D-conformal (n=20, 32.3%) or intensity-modulated radiotherapy (n=42, 67.7%). The median follow-up duration was 34.5 months (range, 9.6-68.8 months). The 6-month CR rate was 96.7%. The 5-year LFFS and progression-free survival rates were 92.0% and 90.4%, respectively. None of the patients experienced grade 3 or worse acute toxicities, and grade 2 acute toxicities were reported in 17 patients (27.4%). CONCLUSION: Reduced-dose RT exhibited excellent response rates in stage IE gastric MALT lymphoma, comparable to historical controls of standard dose (≥ 30 Gy) radiotherapy, with a minimal toxicity profile. Current prospective evidence strongly supports the use of definitive radiotherapy (24-25.5 Gy) for the treatment of H. pylori-independent stage IE gastric MALT lymphoma.

Pragmatic clinical trials for localized prostate cancer: lessons learned and "three sins".

In "Explanatory and Pragmatic Attitudes in Therapeutic Trials", Schwatrz and Lelouch describe two approaches to the design of trials, "… the first "explanatory", the second "pragmatic". They explained "… the biologist may be interested to know whether the drugs differ in their effects … the explanatory approach". Biologically endpoints might determine whether it was better to give androgen deprivation therapy (ADT) before or after external beam radiation (EBRT) (i.e., does the sequence of treatments matter). Alternatively, if the arms focus on a clinical endpoint, this is considered … "the pragmatic approach". An example of a clinically relevant endpoint is overall survival (OS). A real-world example of this are the two randomized controlled trials (RCTs) evaluating the role of prophylactic whole pelvic radiotherapy (WPRT) conducted by the Radiation Therapy Oncology Group (RTOG). RTOG 9413 evaluated possible interactions between the sequence of drugs and volume irradiated, while RTOG/NRG 0924 focuses on OS. There appears to be a common pattern of "what not to do", or "design errors" made by a number of investigators, that I call the "three sins". I posit that the prospects for a well-designed pragmatic RCT are likely to be high if these "three sins" are avoided/minimized. The "three sins" alluded to are: 1. You can't prove something doesn't work by treating people who don't need the treatment. 2. You can't prove something does not work if the treatment is not done properly. 3. You can't prove something does not work with an underpowered study.

Laryngeal Preservation Rate and Salvage Therapy Following Initial Recurrence in a Real-world Setting After Definitive Radiation Therapy in Patients With Locally Advanced Laryngeal Squamous Cell Carcinoma.

Background/Aim: The larynx plays a pivotal role in vocalization and airway protection, and laryngeal cancer manifests through various symptoms. Contemporary strategies focus on laryngeal preservation, particularly through non-surgical modality therapies that utilize radiotherapy. The aim of this study was to assess the laryngeal preservation rate after definitive radiation therapy in patients with locally advanced laryngeal squamous cell carcinoma and investigate salvage therapy subsequent to the initial recurrence in a real-world context. Patients and Methods: Analysis included a total of 40 patients with locally advanced laryngeal squamous cell carcinoma who were treated with definitive radiotherapy in the University of Tokyo Hospital. Treatment involved external beam radiotherapy (70 Gy in 35 fractions) with elective nodal irradiation. The main study outcomes were assessment of survival, overall survival, local control, and the factors influencing laryngeal preservation. Results: The patients exhibited a median age of 64.5 years, and 80% of them were men. Chemotherapy was administered to 82.5% of the patients. The 3-year overall survival, progression-free, and laryngeal preservation survival rates were 86.3%, 66.8%, and 78.4%, respectively. Univariate and multivariate analyses identified chemotherapy to be significantly associated with favorable laryngeal preservation survival (p<0.001). Conclusion: Definitive radiotherapy results in favorable outcomes for laryngeal preservation in locally advanced laryngeal squamous cell carcinoma. This study emphasizes the importance of chemotherapy in comprehensive patient management. Nevertheless, larger prospective studies are crucial to validate and optimize therapeutic approaches for this condition.

Long-term follow-up of unresectable adenoid cystic carcinoma of the trachea and bronchus treated with high-dose proton beam therapy: A report of two cases.

Adenoid cystic carcinoma (ACC) of the trachea is a rare disease that is slow growing and has a risk of distant metastasis. The standard treatment for ACC of the trachea is surgery, but this tumor is often unresectable. In definitive radiotherapy using photons for unresectable ACC of the trachea, it is sometimes difficult to deliver a sufficient dose to the target without exceeding the tolerable dose to the surrounding normal tissues. Here, we report two cases of ACC of the trachea that received a high dose (74 Gy [relative biological effectiveness]) of proton beam therapy and achieved long-term survival.