5-year Disease-free Survival Research Articles

Clinical patterns and outcomes of patients affected by primary malignant melanoma of the oral mucosa: A European multicenter retrospective chart review.

The purpose of this European multicenter study was to describe and assess the characteristics, diagnosis, management, and recurrence of oral malignant melanoma at different European oral and maxillofacial surgery centers. This study was based on a systematic computer-assisted database that allowed the recording of data for all primary oral mucosal melanomas treated in the involved surgical units across Europe between January 1, 2003 and December 31, 2022. The following data were recorded for each patient: gender, age, site, TNM staging, metastases, symptoms, imaging features, histopathological features, treatment, complications, recurrence, follow up, and survival. A total of 29 patients (15 females, 14 males) with a primary oral mucosal malignant melanoma fulfilled the inclusion criteria. The mean age was 64.4 years. The most frequent primary site was the vestibular and crestal maxillary gum. Nineteen patients had been diagnosed with a T3 oral melanoma, nine patients with a T4a oral melanoma, and one patient with a T4b neoplasm. Three patients had distant metastases at diagnosis. Clinically, the most frequently observed clinical features were hyperpigmentation, nodular appearance, ulceration, and hemorrhage. Among the 27 surgical cases, radical/clear margins were obtained in 24 cases, non-radical/invaded margins were obtained in two cases, while in one case a non-specific result of margin positivity was found. The overall 2-year survival was 62%. The 2-year disease-free survival was 52%. Oral mucosal melanoma is an aggressive and often asymptomatic malignancy. The overall long-term survival for patients with oral mucosal melanoma is poor, with a high rate of distant metastasis, independently from the performed treatment. Prevention and early diagnosis could be crucial to improving the disease-free survival of patients with oral mucosal melanomas.

Survival, Tumor Control, and Safety Outcomes of Proton Therapy in Sinonasal Cancer Population: A Systematic Review and Meta-Analysis.

In sinonasal cancer (SNC), treatment with proton therapy (PT) provides excellent local control, especially after gross total resection. Because of the heterogeneity and rarity of this disease site, a comprehensive assessment of toxicity, survival, and control rates is lacking. Our primary objective was to assess the toxicity outcomes of PT in SNC patients, with a secondary aim of assessing survival and tumor control after PT. PubMed, Embase, EBSCO, Scopus, Science Direct, Web of Science, Ovid, Proquest, and Cochrane Library were searched from inception to August 2024 reporting PT acute and late toxicity, survival, and tumor control outcomes in SNC patients. A random-effect meta-analysis was used to assess the pooled safety, survival, and tumor control outcomes. The primary analysis was to report acute and late toxicity. The secondary aims included overall survival (OS), disease-free survival (DFS), local control (LC), regional control (RC), and distant metastasis control (DMC) rate. Fourteen studies were included for qualitative analysis. We pooled data from 756 patients who received PT for SNC. Among acute toxicity (AT), there was a 31.9% occurrence rate of grade ≥ 3 events, whereas within late toxicity (LT), grade ≥ 3 events occurred at a rate of 35.3%. Most LT (62.1%) were classified as grade 2, with the most frequent being ocular (24.8%) or neurological (18.4%) toxicities. The most common grade ≥ 3 toxicities were mucositis (15.3%) in AT and ocular toxicity (9.6%) in LT. The pooled 5-year OS, DFS, LC, RC, and DMC were 36.8%, 34.2%, 35.6%, 28.6%, and 54.3%, respectively. Our analysis demonstrates that PT-treated SNC patients experience acceptable rates of acute and LT consistent with other published outcomes with highly conformal radiation techniques. PT demonstrates favorable OS and DFS. Further prospective and comparative effectiveness research is needed to better quantify the magnitude of the benefit of PT or other forms of radiation modalities.

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.

Impact of TP53 alteration on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndromes.

The poor outcome of TP53 alteration has been reported in myelodysplastic syndrome (MDS) patients. However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in TP53 alteration patients remains debated. Previous studies showed that TP53 mutations had no effect on the prognosis of patients with acute leukemia after haploidentical HSCT (haplo-HSCT). The effect of haplo-HSCT on MDS patients with TP53 alterations remains to be further elucidated. We aimed to reveal the role of TP53 alterations in the prognosis of MDS patients undergoing allo-HSCT, especially haplo-HSCT. 261 MDS patients with known TP53 status were enrolled, including thirty-seven patients with TP53 mutation/deletion (TP53mut/del). TP53mut/del patients showed a worse rate of 2-year cumulative incidence of relapse (CIR) and 2-year disease-free survival (DFS) than TP53 wild type (TP53wt) patients (46.2% vs 17.0%, P < 0.001; 41.8% vs 68.9, P < 0.001) after allo-HSCT, even for those with haplo-HSCT (CIR: P < 0.001; DFS: P = 0.002). However, the prognostic effect of TP53 alteration on overall survival (OS) was not observed in patients with haplo-HSCT (66.7% vs 75.2%, P = 0.108). Positivity of post-transplantation measurable residual disease (post-MRD) and time from diagnosis to transplantation were independent risk factors for MDS patients. TP53 alterations do not affect OS in patients undergoing haplo-HSCT requires further validation.

Host Index and Gallbladder Cancer: An Emerging Prognostic Biomarker.

There is emerging evidence that host related variables predict outcomes in various cancers. The Host index (H-index) incorporates various host-related, blood-derived biomarkers (immunological and nutritional parameters) as a single mathematical formula. The aim of this study was to evaluate outcomes using the H-index as a prognostic marker in gallbladder cancer (GBC) patients undergoing curative resection. Retrospective cohort study of surgically treated GBCs at a tertiary cancer centre from January 2010 to May 2023 was performed. Patients who had received neoadjuvant therapy, metastatic (M1) disease at time of surgical exploration and incidental GBCs were excluded. Baseline neutrophil, lymphocyte, monocyte and platelet counts, hemoglobin and albumin levels were recorded. H-index was computed and analysed. 241 curatively resected GBC patients were included. The H-index was inversely associated with disease free survival (DFS), both on univariate (79.7 vs. 61.4% for H-index </= 1.3 and > 3.4 respectively; p = 0.046) and multivariate analysis (Hazard ratio [HR] for recurrence: 1.954 [95% C.I.: 1.366-2.796]; p = < 0.001). Using the maximally distributed rank statistics, a cut-off of 1.31 showed a significant difference in 3-year DFS (86.2 vs. 68.4% for H-index </= 1.31 vs. > 1.31 respectively; HR: 2.21 [95% CI: 1.16-4.21]; p = 0.013) but not overall survival (OS) (p = 0.269). A higher H-index predicted for worse DFS in curatively resected GBC patients. This shows host related variables do play a role in influencing outcomes in GBC. However, larger prospective studies are required to further strengthen this finding. Host-related, blood derived biomarkers can influence outcomes in various solid tumours. A higher baseline Host index (H-index) value which incorporates various blood-derived biomarkers, predicted for worse disease-free survival in curatively resected gallbladder cancers.

Short- and long-term outcomes of laparoscopic versus open abdominoperineal resection for rectal cancer: A propensity score matching analysis based on 1852 cases.

Randomized studies have demonstrated that laparoscopic abdominoperineal resection is not inferior to open abdominoperineal resection for rectal cancer. Evaluate the immediate and extended results of laparoscopic abdominoperineal resection versus open abdominoperineal resection for rectal cancer. From January 2006 to December 2017, a total of 1852 patients with rectal cancer who had undergone abdominoperineal resection were enrolled in this investigation. The groups were matched in a 1:1 ratio using propensity score matching. The primary endpoints were overall survival and disease-free survival. The secondary endpoints were pathology and short-term postoperative outcomes. Compared to the open abdominoperineal resection group, the laparoscopic abdominoperineal resection group exhibited a higher rate of positive circumferential resection margins (P < 0.001) and fewer postoperative complications (P < 0.001). 5-year disease-free survival (P = 0.449) and overall survival rates (P = 0.664) were comparable. Age (P < 0.001), comorbidity (P = 0.040), (y)pT (P = 0.024), (y)pN (P < 0.001), lymphovascular invasion (P = 0.003) and positive circumferential resection margins (P = 0.014) were independent prognostic risks for overall survival. The pathological outcomes of laparoscopic abdominoperineal resection are inferior compared to open abdominoperineal resection. However, they demonstrate comparable long-term oncological outcomes, and laparoscopic abdominoperineal resection offers certain short-term advantages over the open approach.

Colon and rectal peritoneal carcinomatosis: are we mixing apples with oranges? A propensity score-matched analysis.

Rectal cancer is universally considered a different disease entity as compared to colon cancer, except when dealing with colorectal peritoneal carcinomatosis (PC), in which the two cancers are deemed as the same one. The present study aims to investigate the influence of primary tumor location (colon vs. rectum) on oncologic outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Data from three referral centers undergoing CRS plus HIPEC for PC of colorectal origin were prospectively collected. The primary outcomes were overall survival (OS) and disease-free survival (DFS) according to primary tumor location (colic vs. rectal). Univariate and multivariate analyses were performed using the Cox proportional hazard model first on the total number of patients. Then, a propensity score matching using the nearest-neighbour method with a 1:1 ratio was performed. The study included 167 patients: 126 colic and 41 rectal PC. After propensity score matching, rectal primary tumor location was independently predictive of a lower DFS (HR 1.91; 95%CI 1.06-3.45; p = 0.031) but not of a lower OS (HR 1.12; 95%CI 0.57-2.21; p = 0.73). Post-matching 3-year DFS rates were 49.2% (95%CI 34,3-70,5%) and 19.4% (95%CI 9,4-40,2%) for colic and rectal PC, respectively. The present study shows a significantly worse DFS for rectal cancer PC undergoing CRS and HIPEC compared to colon cancer PC, suggesting a possible need for dedicated pathways for rectal PC patients and posing a question for rectal PC to be considered as a unique disease entity.

« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review.

In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that "augmented RT" schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life. We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after "augmented RT" were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible. Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles. "Augmented RT" reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.

Role of mast cell in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

The pro-tumor effects of mast cell (MC) in the tumor microenvironment (TME) are becoming increasingly clear. Recently, MC were shown to contribute to tumor malignancy by supporting the migration of tumor-associated macrophages (TAMs), suggesting a relationship with tumor immunity. In the current study, we aimed to examine the correlation between MC infiltration and neoadjuvant chemoradiotherapy (nCRT) response for locally advanced rectal cancer (LARC). Ninety-five LARC patients who recieved nCRT were enrolled in this study. Protein levels of the MC marker tryptase and TAM marker CD206 were evaluated with immunohistochemistry (IHC). The correlation between MC infiltration and prognostic factors was evaluated. The effects of MCs on the malignant potential were examined using in vitro proliferation and invasion assays with a colorectal cancer (CRC) cell line (HCT-116). Following nCRT, 31.6% of resected LARC patient specimens were positive for MC infiltration by tryptase IHC analysis. MC infiltration was significantly correlated with nCRT response. The 5-year disease-free survival (DFS) rate was significantly lower in the MC-positive group compared with the MC-negative group (52.3% vs. 76.8%). Univariate and multivariate analyses revealed that MC infiltration was the independent prognostic indicator for DFS. MC infiltration was significantly correlated with CD206 expression, and therefore TAMs. In vitro experiments suggested that tumor activated mast cells could promote CRC cell malignant behavior via production of macrophage inhibitory factor. MC infiltration in LARC patients was positively correlated with TAM infiltration and resistance to nCRT, and was also an independent poor prognostic indicator.

Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67. This study aims to evaluate the accuracy of the MammaTyper® assay in predicting the response of HER2-positive patients to therapy. A well-characterized HER2-positive BC cohort of 287 cases diagnosed at Nottingham University hospitals between 2006 and 2018 was included. The cohort was divided into 2 groups: a trastuzumab-treated group (n=159) and a chemotherapy-only treated group (n=128). Tumor clinicopathologic characteristics were matched between the two groups. Cases with discordant HER2 status were validated through staining of surgical excision specimens. ERBB2 mRNA identified 251/287 (87.5%) cases as HER2-positive, 10.8% (31/287) as HER2 low and 1.7% (5/287) as HER2-negative. According to MammaTyper® assay, ERBB2-positive patients treated with anti-HER2 therapy had significantly prolonged 5-year disease (DFS) and distant metastasis (DMFS) free survival (HR=0.56, p=0.003 and HR=0.62, p=0.023, respectively). MammaTyper®-defined HER2-Enriched subtype showed better response to anti-HER2 therapy compared to IHC-defined subtypes, with significant differences in both 5-year DFS and BCSS (p=0.01 and <0.001, respectively). ERBB2-negative patients did not show survival difference between the group of patients who were treated with trastuzumab and those who were treated with chemotherapy only (p>0.05). Validation analysis revealed that 11/36 ERBB2-negative cases were IHC 2+/ISH positive with very low level of gene amplification and 25 cases were false classified as HER2 positive using current protocols. Combining MammaTyper® assay with IHC to assess HER2 status improves the identification of HER2-positive BC patients who would benefit from anti-HER2 therapy.

A Serial MRI-based Deep Learning Model to Predict Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop and evaluate a deep learning-based prognostic model for predicting survival in locoregionally- advanced nasopharyngeal carcinoma (LA-NPC) using serial MRI before and after induction chemotherapy (IC). Materials and Methods This multicenter retrospective study included 1039 LA-NPC patients (779 male, 260 female, mean age 44 [standard deviation: 11]) diagnosed between April 2009 and December 2015. A radiomics- clinical prognostic model (Model RC) was developed using pre-and post-IC MRI and other clinical factors using graph convolutional neural networks (GCN). The concordance index (C-index) was used to evaluate model performance in predicting disease-free survival (DFS). The survival benefits of concurrent chemoradiation therapy (CCRT) were analyzed in model-defined risk groups. Results The C-indexes of Model RC for predicting DFS were significantly higher than those of TNM staging in the internal (0.79 versus 0.53) and external (0.79 versus 0.62, both P < .001) testing cohorts. The 5-year DFS for the Model RC-defined low-risk group was significantly better than that of the high-risk group (90.6% versus 58.9%, P < .001). In high-risk patients, those who received CCRT had a higher 5-year DFS rate than those who did not (58.7% versus 28.6%, P = .03). There was no evidence of a difference in 5-year DFS rate in low-risk patients who did or did not receive CCRT (91.9% versus 81.3%, P = .19). Conclusion Serial MRI before and after IC can effectively predict survival in LA-NPC. The radiomics-clinical prognostic model developed using a GCN-based deep learning method showed good risk discrimination capabilities and may facilitate risk-adaptive therapy. ©RSNA, 2025.

Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis.

This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78Gy. The median follow-up period was 82months (range: 32-140months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.

Head and Neck Squamous Cell Carcinoma of Unknown Primary-Who Can Be Offered Surgery as the Sole Treatment Modality? A Systematic Review.

Evaluate the role of surgery as the sole treatment modality for patients with cervical head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Systematic review of observational cohort studies with qualitative synthesis. PubMed, Ovid EMBASE, and Cochrane Controlled register of Trials (CENTRAL) were screened from January 2000 up to October 2021. Patients with HNSCCUP after completing diagnostic workup subsequently treated with single-modality surgery. The primary outcome was 3-year overall survival (OS). Secondary outcomes included disease-free survival (DFS), primary emergence, regional recurrence, and distant metastasis. Fourteen eligible studies were identified, including 1780 patients, of whom 294 received surgery as their sole treatment (seven studies) with 3-year OS ranging from 43.9% to 100%. 3-year DFS was reported in four studies (n = 62) ranging from 42.8% to 67.0%. 5-year OS and DFS were available in three studies (n = 31), ranging from 36.6% to 75.0%, and 43.6% to 67.0%, respectively. The rate of primary emergence ranged from 11.1% to 33.3% (seven studies, n = 157), regional relapse from 0.0% to 50.0% (five studies, n = 60) and distant metastasis from 0.0% to 3.3% (three studies, n = 45). Patients undergoing surgery as a sole treatment had predominantly p16/HPV positive N1 (TNM7) disease without ECS. Outcomes for HNSCCUP patients undergoing surgery alone range widely in the literature but may be reasonable in a subset of patients with early-stage p16/HPV positive disease. Data is lacking for p16/HPV negative disease where the potential primary site is more varied and primary emergence appears more common.

Gemcitabine and docetaxel for high-risk non-muscle-invasive bladder cancer: EuroGemDoce group results.

To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment. Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews. Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres. The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols.

Transoral Laser Microsurgery Versus Radiotherapy for T1-T2 Glottic Cancer with Anterior Commissure Involvement: A Systematic Review and Meta-Analysis.

To identify the most effective treatment modality for achieving favorable outcomes in early glottic tumors with anterior commissure involvement (ACI). PubMed, Embase, Web of Science, and ScienceDirect. Random-effects proportional meta-analysis model is used to evaluate the oncological and functional outcomes of transoral laser microsurgery (TLM) versus radiation therapy (RT) in early glottic (T1-T2) cancer with ACI. From a total of 736 studies, 40 studies were included, comprising 2666 early glottic tumor patients with ACI. TLM (52%) and upfront RT (48%) were the primary treatment groups. TLM had better 5-year overall survival (OS) (84.5% [80.3%-88.0%] vs. 79.4% [75.7%-82.7%]). Similarly, TLM-treated patients had better 3-year pooled disease-free survival (DFS) compared with RT-treated patients (82.7% [77.1%-87.1%] vs. 73.3% [23.8%-96.0%]). TLM exhibited a better 5-year local control rate (LCR) than RT (77.2% vs. 71.6%). In our temporal analysis, TLM had a higher 5-year LCR than RT (78.2% vs. 63.5%) in 2001-2012, with similar rates in 2013-2024 (76.8% vs. 78.4%). TLM-treated patients had higher laryngeal preservation rates compared with RT patients (93% [90.6%-94.8%] vs. 87.6% [82.8%-91.2%]). Our meta-analysis is the first in the literature to compare the outcomes between TLM and RT-treated patients with ACI in early glottic tumors. TLM-treated patients appear to have superior 5-year OS and laryngeal preservation compared with upfront RT-treated patients. However, both TLM and RT exhibited comparable oncological outcomes in early glottic tumor patients with ACI during the recent period from 2013 to 2024. Laryngoscope, 2025.

Prognostic role of the pathological status following neoadjuvant chemoradiotherapy and surgery in esophageal squamous cell carcinoma

BackgroundIn this study, we retrospectively examined the prognostic significance of the pathological status of esophageal squamous cell carcinoma (ESCC) patients following neoadjuvant chemoradiotherapy (NCRT) and surgery.MethodsData of patients with cT2-4aN0-3 stage ESCC who underwent NCRT and esophagectomy during 2014–2022 were reviewed retrospectively. Survival differences were compared according to revised TN (rTN) stage (ypT0N0, ypT + N0, ypT0N+, and ypT + N+) using univariate and Cox regression analyses.ResultsOf the 136 patients (59.1 ± 7.2 y) included in this study, 123 (90.4%) were males. There were 39 (28.7%) patients with ypT0N0 disease, 49 (36.0%) ypT + N0, 11 (8.1%) ypT0N+, and 37 (27.2%) ypT + N+. Additionally, 126 patients had a median follow-up period of 30 (1–90) months. The 5-year overall survival was 81.6% in ypT0N0 group, 53.1% for ypT + N0, 50.0% for ypT0N+, and 18.6% for ypT + N+ (p < 0.001) and 5-year disease-free survival was 70.1% for ypT0N0, 39.7% for ypT + N0, 33.3% for ypT0N+, and 18.4% for ypT + N+ (p < 0.001). The ypT + N0 and ypT0N + groups showed no significant differences in survival (p > 0.05). In Cox regression analysis, ypT stage and rTN stage showed an independent association with OS (p = 0.026 and 0.001, respectively). During the follow-up period, 69 (54.8%) patients developed recurrence, with ypT0N0 patients experiencing fewer local and distant recurrences compared to other groups (p < 0.001).ConclusionIn ESCC patients, the ypT0N0 status after NCRT predicts prolonged survival, but this reduces significantly when nodal metastases or residual primary lesions are present.

Long-term Outcomes of Definitive Chemoradiation with Proton Therapy for Treatment of Carcinoma of the Anal Canal: Combined Analysis of Two Prospective Trials.

While definitive chemoradiation (CRT) with 5-FU/MMC remains the standard of care for localized anal cancer, treatment is associated with significant acute and late toxicity. Proton radiation therapy (RT) may potentially reduce such toxicity. Here, we assess the long-term outcomes of anal cancer patients treated with CRT using proton RT in two prospective pilot studies. Patients with stage I-III anal cancer treated with proton RT (pencil beam scanning or intensity modulated proton therapy) per RTOG 0529 dose schema with concurrent 5-FU/MMC (2 cycles) in two prospective, single-arm trials were followed. Loco-regional failure (LRF), distant metastases (DM), colostomy-free survival (CFS), disease free survival (DFS), and overall survival (OS) were assessed. Physician-graded late toxicity (>90 days from CRT) was assessed per CTCAE v4.0. Late toxicities were compared with RTOG 0529 via Fisher's exact test. Patient-reported outcomes (PROs) were analyzed. Between 2013-2020, 39 patients were treated. 37 (95%) patients completed treatment per protocol. Median follow-up was 63 months. 5-year LRF, DM, CFS, DFS, and OS were 21%, 19%, 72%, 69%, and 75%, respectively. Worst late treatment toxicities were G1 in 38%, G2 in 24%, G3 in 19%, G4 in 3%, and no G5. Compared to RTOG 0529, rates of overall G2+ late toxicities were significantly lower (46% vs 75%, p=0.01), attributed to lower dermatologic toxicities (0% vs 25%, p<0.01), but there was no significant difference in overall G3+ toxicities (22% vs 20%, p=1.00). No statistically significant correlations between organ-at-risk dosimetry and late toxicities were noted. Available PROs demonstrated significant proportion of patients had persistent gastrointestinal symptoms at long-term. Definitive CRT with proton RT with concurrent 5-FU/MMC for the treatment of anal cancer resulted in comparable long-term disease control and grade 3+ late toxicities compared to RTOG 0529. Future studies should evaluate additional measures to minimizing treatment toxicity and subsets of patients who are most likely to benefit from proton RT.

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.

Surgical Management of Giant Basal Cell Carcinoma in the Maxillofacial Region: Ablative and Reconstructive Strategies.

Giant basal cell carcinoma (GBCC) is a rare and aggressive subtype of basal cell carcinoma (BCC), characterized by a diameter of ≥5 cm and a potential for deep tissue invasion. This study aimed to present our experience with the surgical management of GBCC in the maxillofacial region, focusing on resection and immediate reconstruction strategies. We conducted a retrospective analysis of 5926 patients with BCC in the maxillofacial region from 2010 to 2020, with a specific emphasis on 32 patients diagnosed with GBCC. Associations between patient and tumor characteristics were analyzed, treatment approaches evaluated, and clinical outcomes assessed. The cohort comprised 20 males (62.5%) and 12 females (37.5%) (P > 0.05), with a median age of 71 years (range: 40-86 years). The median time from tumor onset to presentation was 4 years (range: 2-7 years). A total of 24 GBCCs (75%) developed de novo, whereas 8 (25%) were recurrent BCCs (P < 0.05). The median tumor diameter was 8 cm (range: 5-15 cm), with local invasiveness extending to cartilage in 31.25% of cases, facial muscles in 29.41%, neural tissues in 21.87%, and bone in 18.75%. Surgical resections included orbital exenteration (3 cases, 9.38%), total parotidectomy (2 cases, 6.25%), partial maxillectomy (2 cases, 6.25%), frontal craniofacial resection (2 cases, 6.25%), partial petrosectomy with mastoidectomy (1 case, 3.13%), and near-total rhinectomy (1 case, 3.13%). For reconstruction, a skin graft was used in 3 patients (9.38%), local skin flaps in 15 (46.88%), locoregional flaps in 10 (31.25%), and free flaps in 4 (12.5%). The 5-year overall survival, disease-free survival, and disease-specific survival for the cohort were 87.5%, 93.75%, and 96.88%, respectively. Our findings suggest that a single-stage procedure featuring aggressive surgical resection and reconstruction achieves low complication rates, excellent oncologic control, and acceptable cosmetic outcomes.

Shifting from axillary dissection to targeted axillary surgery after neoadjuvant treatment: the evolving management of occult breast cancer in a monoinstitutional series of 114 patients.

The use of neoadjuvant systemic therapy for primary breast cancer can achieve tumor shrinkage, enabling less invasive surgical treatments, such as breast-conserving surgery instead of mastectomy, and sentinel node biopsy instead of axillary dissection. In recent years, an increasing number of studies have explored the use of primary systemic therapy for occult breast cancer with axillary presentation. These studies suggest that a more conservative approach, involving targeted axillary surgery could be cautiously proposed for occult breast cancer after neoadjuvant chemotherapy in selected patients. In cases where a complete pathological response in the lymph nodes is achieved, there may also be the possibility to omit radiotherapy. We retrospectively reviewed surgical interventions for carcinoma of unknown primary (CUP) syndrome with axillary presentation at the European Institute of Oncology from April 2004 to October 2022. Demographic and clinicopathological characteristics of the patients were collected and follow-up information has been updated. A total of 114 patients who underwent axillary surgery for occult breast cancer were included. The 5-year disease-free survival was 74.5%, while overall survival was 88.5%. A total of 22.8% of patients underwent neoadjuvant treatment. Complete pathological response was achieved in 38.5%. Patients with complete nodal pathological response showed fewer events compared to patients with no complete pathological response after neoadjuvant treatment. Although the sample size is limited, recent advances in breast cancer multimodal treatment indicate that targeted axillary surgery may be considered for the rare clinical presentation of occult breast cancer after neoadjuvant treatment. Trial registration number UID 4184 24/07/2024 "retrospectively registered".