Locoregional Failure Research Articles

The role of external-beam radiotherapy for differentiated thyroid cancer.

The treatment options for differentiated thyroid cancer (DTC) are surgery, thyroid stimulating hormone suppression, radioactive iodine, and multitargeted tyrosine kinase inhibitors. The role of external-beam radiotherapy (EBRT) for DTC is controversial because of the lack of randomized controlled trials, but prospective single-arm studies and propensity score matching analyses have shown its efficacy and safety. This review discusses the role of EBRT after resection of gross disease, when there is a high risk of locoregional failure, as well as its role for locoregionally gross recurrent and unresectable disease. As in other tumor sites, EBRT has an important role in the palliative management and local control of patients with metastatic DTC, especially with bone and brain metastases.

Clinical outcomes, patterns of failure, and salvage therapies of a large modern cohort of patients with anal squamous cell carcinoma treated with definitive-intent IMRT

PurposePatterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy are not well described. Patients and MethodsWe identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure (LRF), distant failure (DF), progression-free survival (PFS), colostomy-free survival (CFS), and overall survival (OS)), patterns of failure, and salvage therapies were collected. Failures were analyzed by competing risks methods, whereas survival endpoints were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months from completing IMRT. Results375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for AJCC stage 0-I, II, and III, respectively. Six-year rates of LRF, DF, PFS, CFS, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse six-year OS than patients without LRF (44% versus 86%, P<0.0001). Approximately 30% of patients who underwent salvage therapy were alive ten years after recurrence, compared with none of the patients who were managed with chemotherapy alone or best supportive care. ConclusionsThis large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Patients with gastroesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastroesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastroesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1:1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg IV every 2 weeks plus ipilimumab 1 mg/kg IV every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, loco-regional and distant failure rates and safety according to NCI-CTCAE v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months (95% confidence interval [CI], 8.4-16.8 months) versus 20.8 months (95% CI, 15.0-29.9 months) for the chemotherapy group, HR 1.55 (95% CI, 1.07- 2.25, one-sided P=0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared to chemotherapy in patients with ypN+ and/or R1 gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

Locoregional control in high-risk neuroblastoma using highly-conformal image-guided radiotherapy, with reduced margins and a boost dose for residual lesions

IntroductionRadiotherapy protocols for high-risk neuroblastoma (HR-NBL) vary across international studies. The purpose of this study was to evaluate the locoregional control in a national HR-NBL cohort treated with highly-conformal image-guided radiotherapy (IGRT), using reduced margins, and a boost dose for residual lesions. Materials and methodsPatients treated with radiotherapy as part of first-line HR-NBL treatment between 2015 and 2022 were eligible. To obtain clinical, internal, and planning target volumes, +0.5 cm, 4DCT-based, and + 0.3/0.5 cm margins, respectively, were added to the edited gross tumour volumes. Prescription dose was 21.6/1.8 Gy, followed by 14.4/1.8 Gy for any residual lesions measuring ≥ 1 cm3 at the time of radiotherapy planning. Intensity-modulated arc therapy was combined with daily cone beam CT-based online patient position verification. Locoregional failure (LRF) rates were compared for the presence of residual lesions < 1 cm3 vs. ≥ 1 cm3 (with/without locoregional activity on nuclear- and MRI[diffusion-weighted imaging]-scans) pre-radiotherapy, age at diagnosis, MYCN-status, [131I]mIBG therapy, response to induction chemotherapy, interval to radiotherapy onset, and metastatic site irradiation. ResultsAmong the 77 included patients, 34 had residual lesions (median volume: 10.0 cm3, IQR 4.8–29.9) with activity visible on 17 nuclear- and 10 MRI-scans. Five-year LRF rate was 7.8 % (95 % confidence interval 1.8–13.8), and not significantly different between those with residual lesions < 1 cm3 vs. ≥ 1 cm3 (6.4 % vs. 14.3 %, respectively, p = 0.27), or any of the other variables. All 6 LRFs (2 isolated, 4 combined) occurred < 1.5 years post-radiotherapy. ConclusionIn HR-NBL, IGRT with reduced margins and a boost dose for residual lesions ≥ 1 cm3 demonstrated excellent locoregional control, comparable to modern literature.

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

ObjectivesThis 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.MethodsFifty-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).ResultsThe 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).ConclusionsIGBT ± 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.

A retrospective study on the comparision of pathological tumour necrosis of conventional versus ultrahypofractionated preoperative radiotherapy in localised extremity soft tissue sarcoma and its correlation with clinical outcomes: A retrospective study on the comparision of pathological tumour necrosis of CONV-RT versus UHYPO-RT preoperative radiotherapy in localised extremity soft tissue sarcoma and its correlation with clinical outcomes

Background and PurposeWe aimed to determine if ultra-hypofractionated radiotherapy (UHYPO-RT) delivering 6Gy x 5 fractions yields similar tumour necrosis compared to conventional radiotherapy (CONV-RT) with 2Gy x 25 fractions in soft tissue sarcoma (STS). The clinical significance of tumor necrosis on loco-regional recurrence-free survival (LRFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Materials and methodsPatients with localised STS treated with CONV-RT or UHYPO-RT followed by surgery were included. Good response was defined as tumour necrosis ≥ 90%, and poor response as < 90%. Mann-Whitney U-test compared median tumour necrosis. Chi-squared analysis was used for categorical variables. Kaplan-Meier function estimated LRFS, DDFS, and OS. ResultsA total of 64 patients received CONV-RT, and 45 received UHYPO-RT. The median tumour size was 7.0 cm, with the lower extremity being the most common site (55%). Myxofibrosarcoma (39%) and undifferentiated pleomorphic sarcoma (16%) were the most frequent histologies. The median time from radiotherapy to surgery was 35 days. There was a significant difference in median tumour necrosis between CONV-RT and UHYPO-RT, with rates of 40% and 60%, respectively (p = 0.022). Patients receiving UHYPO-RT had a higher percentage of tumour necrosis at the 90% cutoff, achieving 27% compared to 6% for CONV-RT (p = 0.003). In a median follow-up of 32 months, 12 patients (9%) experienced loco-regional recurrence, 24 patients (19%) faced distant failure, and 19 patients (15%) died from metastatic disease. Patients with < 90% necrosis had higher rates of loco-regional (13% vs. 0%, p = 0.207) and distant failure (25% vs. 0%, p = 0.021). Three-year LRFS was 86% for < 90% necrosis and 100% for ≥ 90% necrosis (p = 0.160). DDFS was 75% for < 90% necrosis versus 100% for ≥ 90% (p = 0.036). OS rates were 79% and 93%, respectively (p = 0.290). ConclusionPreoperative RT with UHYPO-RT was associated with a higher rate of tumour necrosis ≥ 90% than CONV-RT. Our data suggest that more extensive necrosis is associated with better clinical outcomes.

Tumor Hypoxia on 18F-fluoromisonidazole Positron Emission Tomography and Distant Metastasis From Head and Neck Squamous Cell Carcinoma.

Given high rates of locoregional control after definitive management of head and neck squamous cell carcinoma (HNSCC), better methods are needed to project distant metastasis (DM) risk. Tumor hypoxia on 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is associated with locoregional failure, but data demonstrating an association with DM are limited. To determine whether tumor hypoxia on FMISO PET is associated with DM risk after chemoradiotherapy (CRT) for HNSCC. This cohort study assessed patients with HNSCC enrolled in 2 prospective clinical trials at a single academic referral center from 2004 to 2021 in which participants received FMISO PET before and during CRT. Data analysis occurred from May 2023 to May 2024. FMISO PET scans before and 1 to 2 weeks after starting CRT were evaluated for tumor hypoxia by nuclear medicine physicians. The primary outcome was DM, defined as biopsy-proven HNSCC outside the primary site and regional lymph nodes. Time to DM was modeled with competing risk regression, with death as a competing risk. Overall survival (OS) was assessed secondarily and modeled with Cox regression. Among 281 patients (median [range] age at CRT, 58.7 [25.5-85.6] years; 251 male [89.3%]) included in this study, 242 (86.1%) had oropharyngeal primary cancer, and 266 (94.7%) had human papillomavirus-positive disease. Of all patients, 217 (77.2%) had T stage 1 or 2, and 231 patients (82.2%) had N stage 2b or less. De-escalated 30 Gy CRT was delivered to 144 patients (51.2%), and the remainder received standard 70 Gy CRT. On FMISO PET examination, 73 patients (26.0%) had hypoxia-negative disease before CRT, 138 patients (49.1%) had hypoxia-positive disease before CRT and then hypoxia-negative disease during CRT, and 70 patients (24.9%) persistently had hypoxia-positive disease before and during CRT. At a median (IQR) 58 (46-91) months of follow-up, 12 DM events and 22 deaths were observed. Persistent intratreatment hypoxia was associated with increased DM risk (hazard ratio, 3.51; 95% CI, 1.05-11.79; P = .04) and worse OS (hazard ratio, 2.66; 95% CI, 1.14-6.19; P = .02). No patients with hypoxia-negative disease before CRT experienced DM. In this cohort study using pooled analysis of prospective nonrandomized clinical trials incorporating FMISO PET in the definitive management of HNSCC, persistent intratreatment hypoxia was associated with increased risk of DM and worse OS. Conversely, all patients with hypoxia-negative disease before treatment remained free of DM. These findings suggest that pretreatment and intratreatment FMISO PET results may serve as biomarkers for DM risk and aid in identifying candidates for escalated therapeutic strategies.

Association of MORC2 expression with progression-free survival in cervical cancer patients treated with concurrent chemoradiotherapy.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.

Non-irradiated area of intraoperative radiotherapy with electron technique: outcomes and pattern of failure in early-stage breast cancer from a single-center, registry study

IntroductionIntraoperative radiotherapy (IORT) with electrons has revealed to have higher rates of ipsilateral breast tumor recurrence (IBTR) than external beam radiotherapy in updated large-scale, randomized controlled trials in 2021. This study details the oncological outcomes of IORT with electron beams using our strict IORT policies. We have found new and important observations regarding the location of recurrence.Methods and materialsThis is a single institution registry of early-stage breast cancer patients who underwent lumpectomy and electron beam IORT with appropriate cone size. All patients met our pre-excision requirements. The primary endpoint was 5-year IBTR rate, with secondary endpoints being 5-year locoregional failure rate, 5-year distant metastasis rate, 5-year overall survival and, importantly, the failure patterns.ResultsBetween January 2011 and December 2022, 124 patients were recruited. The median follow-up was 6.7 years. The 5-year IBTR rate was 1.87% (95% CI 0.47–7.29%), which is much lower than the ELIOT trial and comparable with other accelerated partial breast irradiation (APBI) techniques. The 5-year locoregional failure rate was 3.68% (95% CI 1.40–9.52%), and the 5-year distant metastasis rate was 0.88% (95% CI 0.13–6.12%), while the 5-year overall survival rate was 97.52% (95% CI 92.44–99.19%). Six patients experienced IBTR. All recurrences were in surgical area, occurring superficial to the tumor bed and within 1 cm of the skin dermis. This failure pattern is very unique and might be explained by our hypothesis of the non-irradiated area beneath the skin.ConclusionsIORT with electron beams with strict patient selection criteria and strict large cone size is still an acceptable treatment for select patients with early-stage breast cancer. However, our new findings support extreme caution in the non-irradiated area beneath the skin around the tumor cavity. Given the constraints of our sample size, these findings should be interpreted cautiously and warrant further investigation in larger, more comprehensive studies.

Randomized clinical trial on accelerated preoperative hyperfractionated radiotherapy versus preoperative hyperfractionated radio-chemotherapy in locally advanced rectal cancer.

The aim of this study was to compare pathological response rates after preoperative hyperfractionated radiotherapy with co-administration of chemotherapy based on 5FU (HART-CT) versus preoperative hyperfractionated radiotherapy (HART) in patients with resectable rectal cancer. Patients with T2/N+ or T3/any N rectal cancer were randomized either to HART twice a day (28 fractions of 1.5 Gy) to total dose 42 Gy or to HART-CT. Tumour regression grade was postoperatively assessed according to the 4-point scale as recommended by the American Joint Committee on Cancer (AJCC). The secondary endpoints included overall survival (OS), disease-free survival (DFS), toxicity of preoperative treatment, locoregional, and distant failure rates. There were 187 patients eligible for analysis: 95 in HART and 92 in the HART-CT. Median follow-up was 5.6 years. The analysis demonstrated a significantly higher chance of achieving pathologic complete response in HART-CT arm: complete response was achieved in 4/95, 4% (HART) and 11/92, 12% (HART-CT) (P = .045). The differences in OS and DFS, while tending to favour HART-CT, were not significant: OS (P = .13, hazard ratio [HR] = 0.82, 95% CI, 0.63-1.06) and DFS (P = .32; HR = 0.88, 95% CI, 0.69-1.13). The locoregional failure and distant metastases rates did not statistically differ between the trial arms. The rate of late complications was similar (P = .51), grade 3+ being 8% versus 11% in the HART/HART-CT group, respectively. The hyperfractionated preoperative radiotherapy with concurrent 5-Fu-based chemotherapy (HART-CT) improved pathological response rate compared to HART. This translated into favourable OS and DFS in HART-CT, but the differences did not reach the threshold for significance. A new hyperfractionated chemo-RT scheme is proposed. Histopathological major response (TRG 0-1) is associated with better clinical outcome.

Definitive Radiation Therapy is a Viable Treatment for Locally Advanced Basal Cell Carcinoma Otherwise Requiring Radical or Disfiguring Resection

BackgroundStandard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiotherapy for locally advanced BCC in the contemporary era are not well established. ObjectiveWe sought to determine locoregional control and disease specific survival after definitive radiotherapy for locally advanced BCC. MethodsPatients with locally advanced BCC treated with definitive radiotherapy between 2005-2020 from 4 academic tertiary care institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where margin negative resection would lead to unacceptable cosmetic or functional deficit. Additionally, a set of 5 risk factors (size ≥4 cm, the presence of bone invasion, PNI, immunocompromised patient, and recurrent disease) was separately defined and outcomes were investigated. Results608 locally advanced BCC cases were identified, of which 140 were treated with definitive radiotherapy. Median follow up was 22.9 months (1.5-207.2 months). 101 (72.1%) tumors were treated with upfront definitive radiotherapy, while 39 (27.9%) were treated for a recurrence. 5-year Kaplan-Meier estimated locoregional control was 78%. The majority of locoregional failures were local recurrences (95.5%). Larger tumor diameter was a risk factor for locoregional failure (p=0.045), while recurrent disease was not (p=0.29). Cumulative incidence of BCC related mortality at 5 years was 9.5%. Patients with 0 risk factors had a 5-year FF-LRF of 92.4%, whereas those with 1+ risk factors had a 5-year FF-LRF of 68.5% (p=0.004). ConclusionDefinitive radiotherapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study.

Weekly Image Guidance in Patients With Cervical Cancer Treated With Intensity-Modulated Radiation Therapy: Results of a Large Cohort Study.

Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients. The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities. IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

1234: UICC, but not, can identify high risk of locoregional failure as good as our multi-endpoint model

1234: UICC, but not, can identify high risk of locoregional failure as good as our multi-endpoint model

Outcomes of Watch-and-Wait Versus Abdominoperineal Resection in Lower Rectal Adenocarcinoma Post Neoadjuvant Therapy: An Iraqi Cohort Study.

Rectal malignancy ranks among the most prevalent malignancies in humans. Neoadjuvant chemoradiotherapy (nCRT) is advocated as the standard treatment for locally advanced rectal cancer. In patients who achieve complete clinical response (cCR), successive surgical intervention may result in favorable immediate and long-lasting results; however, itmay be associated with decreased quality of life. This study aims to evaluate the incidence of local recurrence in rectal adenocarcinoma between patients who underwent a watch-and-wait approach and those who underwent abdominoperineal resection following the achievement of a cCRafter nCRT. This is ananalytic cohort study that included 68 patients and was conducted in Baghdad Teaching Hospital/Medical City, Baghdad. The data were collected from the 1st of April 2021 to the 1st of October 2023. All patients with stage II and III rectal adenocarcinoma who achieved cCR after receiving nCRTwere included in the study. There was no statistically significant difference between the two study groups regarding non-regrowth disease-free survival (p-value = 0.708). Cox-regression multivariate analysis revealed that baseline T stage and serum carcinoembryonic antigen (CEA) were significantly associated with locoregional failure. The present study reveals that implementing the watch-and-wait strategy had the benefit of avoiding major surgery, stoma, and their complications without coming at the cost of reduced locoregional recurrence.

Pre-treatment magnetic resonance imaging in anal cancer: large-scale evaluation of mrT, mrN and novel staging parameters

BackgroundIn patients with squamous cell carcinoma of the anus (SCCA), magnetic resonance (MR) imaging is recommended for pre-treatment staging prior to chemo-radiotherapy (CRT), but large-scale evaluation of its staging performance is lacking.MethodsWe re-characterised pre-treatment MRs from 228 patients with non-metastatic SCCA treated consecutively by CRT (2006–2015) at one UK cancer centre. We derived TN staging from tumour size (mrTr) and nodal involvement (mrN), and additionally characterised novel beyond TN features such as extramural vascular invasion (mrEMVI) and tumour signal heterogeneity (mrTSH). Primary outcomes were 5-year overall survival (OS) and 3-year loco-regional failure (LRF). Time-to-event analyses used Kaplan-Meier estimates; Hazard Ratios (HRs) with confidence intervals (CIs) were derived from Cox models.ResultsWith a median follow up of 60.9 months, 5-year OS was 74%. Poor OS was associated with increasing mrT (HR: 1.12 per cm [95% CI: 1.07–1.33]), nodal positivity (HR 2.08 [95% CI 1.23–3.52]) and mrEMVI (HR 3.66 [95% CI: 1.88–7.41]). 3-year LRF rate was 16.5%. Increased LRF was associated with increasing mrT (HR: 1.43 per cm [95% CI: 1.26–1.63]), nodal positivity (HR 2.70 [95% CI 1.39–5.24]) and mrTSH (HR 2.66 [95% CI 1.29–5.48]).ConclusionsIn SCCA, the study demonstrates that mrT and mrN stages are prognostic, while mrEMVI and mrTSH may be novel prognostic factors.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Definitive Chemoradiotherapy versus Trimodality Therapy for Locally Advanced Esophageal Adenocarcinoma: A Multi-Institutional Retrospective Cohort Study.

The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.

“Mid-P strategy” versus “internal target volume strategy in locally advanced non small cell lung cancer: Clinical results from the randomized non-comparative phase II study Mid-P

BackgroundLocally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of “Mid-position” (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. MethodsThis prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. ResultsAmong 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. ConclusionLocal control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.

Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study

BackgroundThe National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin.MethodsOur institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan–Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event.ResultsAmong 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8–65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58–5.47, p < 0.001) and progression-free survival (aHR 2.32, 95% CI 1.29–4.17, p = 0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19–17.3, p = 0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46–5.58, p = 0.46). KPS < 90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10–6.65, p = 0.03).ConclusionOur study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

Pattern of LRR in Endometrial Cancer and Identification of Predictive Factors

Background: Tailored adjuvant treatment is key to managing endometrial cancer effectively. Understanding prognostic factors of loco-regional failure and the impact of adjuvant treatment can help in treatment de-escalation without compromising survival outcomes. The aim of this study was to assess the pattern of failure in endometrial cancer patients and to determine predicting Loco-Regional Recurrence (LRR) factors. Patients and methods: Data were collected from 214 patients treated for endometrial cancer between 2005 and 2012 in Salah Azaiez Institute in Tunisia. All patients underwent upfront surgery followed by adjuvant brachytherapy with or without external beam radiation. The median follow-up period was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors for LRR. Results: The 5-year overall survival rate was 78.1%, and the 5-year progression-free survival rate was 80.1%. LRR occurred in 25 patients (11.6%), with a median recurrence time of 29 months (range 4 months - 46 months). Pelvic relapse was the most common site, occurring in 10 patients. Vaginal relapses were observed in 9 patients, and retro-peritoneal relapses were observed in 6 cases. FIGO stage, tumor grade, histologic type, Lympho-Vascular Space Invasion (LVSI), and delays in adjuvant treatment were significant predictors of LRR. Conclusion: Identifying prognostic factors for LRR in endometrial cancer is crucial for optimizing adjuvant treatment strategies. Higher FIGO stages and the presence of LVSI were independent predictive factors for LRR. Tailored adjuvant treatment, taking these prognostic factors into account, is essential to improve patient outcomes and minimize unnecessary treatment-related toxicity.