Search Results (115)

Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [¹⁸F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [¹⁸F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article

Background/Objectives: High-grade endometrial cancer, including non-endometrioid and grade 3 endometrioid histologies, is associated with poor prognosis despite early-stage diagnosis. This study assessed the prognosis of early-stage high-grade endometrial cancer, identified prognostic factors, and evaluated the optimal candidates for adjuvant therapy. Methods: We retrospectively analyzed 106 patients with 2018 FIGO stage I–II high-grade endometrial cancer who underwent hysterectomies between 2008 and 2022. Adjuvant therapy was determined by a multidisciplinary team. Survival outcomes were evaluated using the Kaplan–Meier method and Cox regression model. Results: Of 106 patients, 60 had non-endometrioid, and 46 had grade 3 endometrioid carcinoma; 69 (65.1%) received adjuvant therapy. After a median follow-up of 48.8 months, 37 patients experienced disease progression, and 21 died. Non-endometrioid histology was significantly associated with worse overall survival (p = 0.002). Lack of lymph node dissection, deeper invasion, and the omission of adjuvant therapy were additional adverse prognostic factors. Adjuvant therapy improved the overall survival (p = 0.009), disease-free survival (p = 0.021), and locoregional recurrence-free survival (p = 0.034) in patients with one or two risk factors. Conclusions: Non-endometrioid histology, deep invasion, and the lack of lymph node dissection are associated with worse survival in early-stage high-grade endometrial cancer. Adjuvant therapy should be considered in patients with these risk factors. Full article

Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents. Full article

Introduction: Ampullary adenocarcinomas (AMPACs) represent rare malignant neoplasms arising in the Ampulla of Vater. Due to a lack of prospective studies and heterogeneous results from retrospective analyses, the outcomes of adjuvant chemotherapy (AC) in AMPAC are unclear. Methods: Pooled, pseudonymized data were retrieved from clinical cancer registries participating in the German Cancer Registry Group of the Association of German Tumor Centers (GCRG/ADT). Patients who underwent surgical resection of AMPACs (ICD-10: C24.1) with subsequent follow-up or AC were included. Patients with 90-day postoperative mortality were excluded. The epidemiologic and histopathologic features as well as the overall survival and recurrences were compared in both groups using R statistics. Results: In total, 830 patients with AMPACs were identified, of which 184 (22.2%) received AC. The surgery + AC patients showed more advanced tumor stages and more pronounced locoregional invasion as compared to the group undergoing surgery alone. AC was independently associated with an improved overall survival (OS) in a multivariable analysis (HR 0.57, p < 0.001), where pT3-4 status, lymph node metastases, vascular invasion, and advanced grading remained independent prognostic factors for OS. In the subgroup analyses, AC was associated with improved OS in the patients with pT3-4 tumors, lymph node metastases, lymphovascular invasion, and advanced grading, or UICC stage III, whereas no association with the OS was observed in the other subgroups. AC was also associated with superior disease-free survival (DFS) in a multivariable analysis. Conclusions: We provide a large-scale population-based analysis of AMPAC patients, showing an association of AC with improved OS in patients with advanced-staged disease or signs of locoregional invasion as compared to surgery alone. Full article

Background: A previous published Phase 2 trial using 2–4 doses of neoadjuvant cemiplimab in stage II–IV resectable cutaneous squamous cell carcinoma (CSCC) demonstrated that a complete pathological (pCR) rate of 51% and major pathological response (mPR) rate of 13% could be achieved with durable disease control. Methods: In this open-label, single-institution phase II trial (NCT05878288), patients with stage II–IV resectable CSCC received up to four doses of neoadjuvant cemiplimab prior to surgery. The primary endpoint of the study was to perform comprehensive molecular profiling. The focus of this report are the secondary clinical endpoints of pCR rate, mPR (defined as <10% viable tumour) rate, overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, immune-modified RECIST (imRECIST) and Immune PET Response Criteria in Solid Tumours (iPERCIST), disease-free survival (DFS), overall survival (OS), safety, and to describe changes in planned surgery. Results: Eleven patients were enrolled, with all proceeding with surgery. An ORR and pCR rate of 73% (8/11; 95% CI 0.39–0.93) was achieved, whilst 3/11 patients progressed on treatment. On pre-operative imaging, all 8/11 pCR patients demonstrated a partial response (RECIST 1.1), whilst 6/8 achieved a complete metabolic response and 2/8 a partial metabolic response (iPERCIST). Median follow-up was 10.2 (IQR 6.7–16.4) months. DFS was 91% (95% CI 0.57–1) and OS was 100% (95% CI 0.68–1), with one non-responder patient who developed recurrent locoregional and distant metastatic disease. There were no unexpected safety signals. Pathological features of response to neoadjuvant immunotherapy most commonly were granulomatous inflammation with keratin, fibrosis and inflammation. No cases with a dense inflammatory infiltrate were observed. Neoadjuvant immunotherapy did not impact the intra-operative planning and execution of surgery, but in the eight pCR cases, it reduced the extent of required surgery, whilst in the three non-responder cases, surgery was more extensive than originally planned. Conclusions: The DISCERN trial confirms that an excellent complete response rate can be achieved with four doses of neoadjuvant immunotherapy in stage II–IV CSCC. Proposed refinements to the pathological assessment of response and metabolic response criteria in CSCC for the neoadjuvant context are provided. Full article

Background: Liver transplantation (LT) is regarded as a curative approach for patients with hepatocellular carcinoma (HCC), especially those with underlying advanced liver disease. However, the recurrence of HCC post-LT poses significant challenges, with reported rates of 15–20% within the first two years following surgery. Effective management of single-nodule recurrence is critical to improving patient outcomes. Methods: This meta-analysis evaluates the efficacy of surgical resection versus locoregional therapies (LRT) in patients with localized HCC recurrence after LT. We adhered to the PRISMA Statement in conducting a thorough search of relevant studies published from 2009 to 2024, ultimately including ten studies that met our eligibility criteria. Results: The results indicate that patients undergoing surgical treatment displayed superior one-year overall survival (OS) rates compared to those receiving LRT (71% vs. 62%, p = 0.038), as well as higher one-year disease-free survival (DFS) rates (60% vs. 54%, p = 0.042). Notably, patients in the LRT group presented with more advanced HCC characteristics prior to transplantation, including higher rates of microvascular invasion and elevated alpha-fetoprotein levels. Conclusions: Our findings suggest that while surgical resection is associated with better survival outcomes, the choice between surgical and locoregional approaches must be individualized based on tumor characteristics and liver function. The ongoing development of standardized guidelines with the inclusion of immunotherapy or targeted agents will be essential in refining treatment pathways and improving outcomes for patients experiencing HCC recurrence following LT. Full article

Background/Objectives: The objective was to compare the results of segmentectomy and lobectomy in the treatment of c-stage IA lung cancer in terms of tumor recurrence and 5-year survival. Methods: An observational study was performed using 3533 patients included in the registry of the Spanish VATS Group (GEVATS) of the Spanish Society of Thoracic Surgery (SECT) between 2016 and 2018. A total of 1004 lobectomies and 83 segmentectomies in c-stage IA were selected. Two comparable groups were selected through 2:1 propensity score matching with patient-, tumor- and surgery-related variables, leaving 166 lobectomies and 83 segmentectomies. Tumor recurrence was analyzed by Fisher’s test and overall, cancer-specific, recurrence-free and disease-free survival by Kaplan-Meier and Log-rank tests. Results: Overall recurrence was 23.7% in both groups, with a predominance of locoregional recurrence in segmentectomy (16.2% vs. 11.2%) and distant recurrence in lobectomy (12.5% vs. 7.5%). There was no difference between the two groups in any of the survival types. Overall survival at 5 years was 73.5% (95% CI: 65.5–82.4%) in the lobectomy group vs. 73.1% (95% CI: 60.1–88.9%) in the segmentectomy group. Conclusions: Anatomic segmentectomy may be a valid option in the treatment of c-stage IA lung cancer since the recurrence and long-term survival outcomes compared to lobectomy are equivalent. Full article

Background: Implant-based breast reconstruction (IBBR) following conservative mastectomy is the most common approach for women undergoing breast cancer surgery. The aim of this study was to compare the oncological outcomes of conservative mastectomy combined with prepectoral IBBR to the subpectoral technique. Methods: The clinical and demographic data of consecutive breast cancer patients who underwent conservative mastectomy with either prepectoral or subpectoral IBBR between January 2018 and December 2023 were retrospectively analyzed. The primary outcome was the impact of conservative mastectomy with prepectoral IBBR on local recurrence-free survival (LRFS). Secondary outcomes included distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 842 women (with a median age of 46 years and a range of 20–79 years) were included in the study. Of these, 648 patients (77.0%) underwent prepectoral IBBR, while 194 (23.0%) received subpectoral IBBR. The median follow-up was 32 months (3–74). Locoregional relapse occurred in 19 patients (2.9%) in the prepectoral group and 14 (7.2%) in the subpectoral group. Distant metastases were observed in 21 (3.2%) patients in the prepectoral group and 11 (5.7%) in the subpectoral group. Deaths were reported in eight patients (1.2%) in the prepectoral group and five (2.6%) in the subpectoral group. There were no statistically significant differences between the two groups in terms of the LRFS, DDFS, and OS (p = 0.676; p = 0.994; p = 0.940, respectively). Conclusions: Our study indicates that conservative mastectomy combined with prepectoral IBBR produces similar results to those of the subpectoral approach, with no significant differences in LRFS, DDFS, and OS. Full article

Background/Objectives: Loco-regional recurrence (LRR) of esophageal cancer following esophagectomy presents a significant therapeutic problem. This study aimed to evaluate the effectiveness of salvage concurrent chemoradiotherapy (CCRT) and to identify the prognostic factors influencing the survival outcomes in patients with an LRR of esophageal cancer. Methods: This retrospective study included 68 patients who underwent salvage CCRT for an LRR of esophageal squamous cell carcinoma between April 2008 and June 2024. Patients were treated with either 50.4 Gy in 28 fractions or 60 Gy in 30 fractions, along with concurrent fluoropyrimidine- and platinum-based chemotherapy. Prognostic factors were identified using univariate and multivariate Cox proportional hazards models. Results: The median overall survival (OS) was 30.1 months (95% confidence interval [CI]: 21.5–110.7 months), with a 2-year OS rate of 57.4%. The median progression-free survival (PFS) was 8.9 months (95% CI: 6.3–17.7 months). In the multivariate analysis, the significant prognostic factors for OS included the interval to recurrence (>1 year vs. ≤1 year, hazard ratio [HR] = 2.307, p = 0.024) and radiotherapy dose (60 Gy vs. 50.4 Gy, HR = 2.414, p = 0.040). For PFS, the interval to recurrence and radiotherapy dose remained significant predictors (p < 0.05). The 2-year OS rate was higher in the 60 Gy arm (62.7% vs. 42.0%, p = 0.285) and in patients with recurrence occurring >1 year after surgery (73.4% vs. 29.9%, p = 0.0054). The local control rate at 2 years was 71.9%, with better outcomes observed in the 60 Gy arm (93.5% vs. 76.5%, p = 0.0651). Conclusions: Salvage CCRT is a viable treatment option for LRR of esophageal cancer, achieving favorable survival outcomes, particularly in patients with late recurrence (>1 year) and in those receiving higher radiotherapy doses. Full article

Background: Medullary thyroid cancer (MTC) is a heterogeneous disease. While the International MTC Grading System (IMTCGS) provides baseline risk stratification, it lacks therapeutic relevance. In several cancers, EZH2 overexpression harbors an adverse prognosis, with several EZH2 inhibitors undergoing investigation. This study validated the IMTCGS and examined the prognostic value of EZH2 and other biomarkers. Methods: Clinical data were collected and MTC specimens were retrospectively reviewed and morphologically assessed. Immunohistochemistry (IHC) of Ki-67 allowed IMTCGS validation. IHC of EZH2, PD-L1 and PSMA was evaluated on a tissue microarray (TMA). Results: Of 64 MTCs, the median tumor size was 28 mm (IQR 15–40). Coagulative necrosis, ≥5 mitoses, and Ki-67 ≥ 5% was seen in nineteen (30%), three (5%) and seven (11%) cases. Median Ki-67 was 0.9% (IQR 0.4–2.1). Forty-three (67%) and twenty-one (33%) were classified as IMTCGS low- and high-risk, respectively. High-risk tumors were associated with lower distant metastasis-free survival (DMFS) (HR 5.651, p = 0.017), locoregional recurrence-free survival (LRFS) (HR 18.323, p < 0.001) and disease-specific survival (DSS) (HR 10.001, p = 0.002), but not with overall survival (OS) (HR 2.109, p = 0.146). EZH2 expression was identified in 39/46 (85%) cases on the TMA. An expression of ≥10% (9/46, 20%) was predictive for DMFS (HR 4.747, p = 0.030), LRFS (HR 4.242, 0.039), DSS (HR 19.736, p < 0.001) and OS (HR 8.386, p = 0.004). PD-L1 and PSMA had no prognostic value. Conclusions: This study validates the prognostic value of the IMTCGS and identifies EZH2 as a novel prognostic biomarker in MTC patients. The therapeutic potential of EZH2 warrants further investigation in larger cohorts. Full article

Background: Intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) is used in the breast cancer (BC) treatment for years now to obtain homogeneous dose distribution in the treated volumes and reduce the doses to organs at risk. The purpose of this study was to evaluate our experience in terms of local control, overall survival, progression free survival and adverse events in BC patients treated with IMRT-HT with long term follow-up. Methods: This study is a retrospective data analysis of patients irradiated with IMRT-HT. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups of the population. Long-term toxicities including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the independent predictors of the side effects. Results: Between 2009 and 2015, a total of 194 breasts in 179 women with nonmetastatic breast cancer were treated. Most of the tumors were grade III and N+. With a median follow-up of 10 years, we observed 9 local recurrences, 2 loco-regional recurrences, and 29 patients experienced metastatic disease. Only 18 patients are dear, of them 7 cases with breast cancer death. At 10 years, the Local recurrence free survival was 95.3% [95%CI: 92.1–98.5], the loco-regional relapse free survival was 94.5% [91.1–98.1]. The metastases free survival was 82.9% [76.9–89.3]. The progression free survival was 79.9 [73.6–86.7]. The cancer specific survival was 94.3%, and the overall survival 88% [82.8–93.5]. At long term, there were no cardiac, lung, thyroid, digestive radio induced toxicities. A small number of patients experienced grade I or II fibrosis. Conclusions: IMRT-HT could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy. IMRT-HT provides favourable long-term prognosis, while late toxicity is acceptable. Full article

Neoadjuvant chemoradiation therapy (NCRT) is an underutilized treatment in breast cancer but may improve outcomes by impacting the tumor immune microenvironment. The aim of this study was to evaluate NCRT’s impact on recurrence and the role of tumor-infiltrating lymphocytes (TILs) in treatment response. We hypothesized that NCRT reduces recurrence by upregulating TILs. Patients with locally advanced breast cancer (LABC) were treated with NCRT. Stage IIB to III patients with any molecular subtypes were eligible. The patients were matched for age, stage, and molecular subtype by a propensity score to a concurrent cohort receiving standard neoadjuvant chemotherapy (NCT) followed by adjuvant radiation. The objective of this study was to assess the patients in terms of the pathological complete response (pCR), TIL counts prior to and following treatment, and locoregional recurrence. The median follow-up was 7.2 years. Thirty NCRT patients were successfully matched 1:3 to ninety NCT patients. The NCRT cohort had no regional and locoregional recurrences (p = 0.036, (hazard ratio) HR [0.25], 95% confidence interval (CI) [0.06–0.94] and p = 0.013, HR [0.25], 95% CI [0.08–0.76], respectively), compared to 17.8% of the NCT cohort. The NCRT group had significantly more pCRs, and TILs were increased in the post-treatment pCR specimens. NCRT can improve outcomes in LABC patients, with a higher pCR and significantly lower locoregional recurrence/higher recurrence-free survival. Further trials are needed to evaluate the role of NCRT in all breast cancer patients. Full article

Although the majority of patients with nasopharyngeal carcinoma (NPC) present with early-stage or locoregional disease that can be treated with definitive radiotherapy, approximately 20% of patients experience disease recurrence, and 15% present with metastatic disease that is not amenable to curative therapy. Management of patients with recurrent or metastatic (r/m) NPC who are not candidates for local salvage therapy is challenging in Canada, as there is uncertainty in extrapolating evidence that is largely generated from Southeast China to non-endemic regions such as Canada. Currently, treatment options in Canada are limited to chemotherapy regimens that can only achieve short-term response and prolongation of survival. The addition of anti-PD-1 monoclonal antibodies to chemotherapy has been shown to extend progression-free survival in recurrent r/m NPC compared to chemotherapy alone; however, approval of PD-1 inhibitors in Canada has lagged behind other jurisdictions where NPC is non-endemic. This paper reviews the current systemic treatment landscape for r/m NPC in Canada, highlights unmet treatment needs for patients who are not candidates for curative therapy, and discusses the challenges and opportunities that lie in emerging therapies. Full article

Background: With greater awareness and increased screening, cancers are increasingly being diagnosed at stage I. Women with these small node-negative tumours have excellent survival prospects after surgery, but many women, especially those with triple-negative and human epidermal growth factor receptor (HER)-2-positive tumours, still receive adjuvant systemic treatments to reduce the recurrence risk. Aims: We review the outcomes of women diagnosed with stage I (T1N0M0) tumours in our unit and examine the effect of systemic chemotherapy with/without targeted therapy on recurrence patterns and survival outcomes. Results: We reviewed 643 women diagnosed with T1N0M0 disease over a 10-year period. Five-year recurrence-free survival (RFS) was 96.6% and the 10-year RFS was 95.5%. Recurrence occurred in 4.7% of the women and was limited to locoregional sites in two-thirds of the instances. Systemic recurrences developed in 12 women, all of whom had ER-positive/HER2-negative disease. The mode of surgery emerged as the only independent predictor of recurrence. Recurrence was highest in women treated with wide local excision (WLE) alone (p < 0.05), but not in those who had received breast radiation after WLE (p = 0.112). Systemic chemotherapy, with or without anti-HER2 therapy, was discussed with 334 women, of whom 50.6% received the treatment; these women were more often younger and had triple-negative or HER2-positive tumours (p < 0.001). Women who received chemotherapy showed a non-significant tendency to develop locoregional recurrence (p = 0.104), but the number of systemic recurrences were similar to those documented in women who had not received chemotherapy. Chemotherapy and/or targeted treatment was not observed to have a significant effect on 5-year recurrence-free survival (p = 0.444). Conclusions: Stage I cancers have excellent survival outcomes. An optimal local surgical treatment is important and we did not find chemotherapy and/or targeted therapy to produce any significant differences in survival. Full article

Objectives: In this paper, we investigate the association of glycoprotein 96 (GP96) and androgen receptor (AR) expression with clinicopathological factors, additional axillary lymph node burden, and their potential role in predicting 5-year overall survival (OS) and disease-free survival (DFS) in breast cancer (BC) patients with sentinel lymph node (SLN) involvement. We also explore the prognostic value of the presence of extranodal extension (ENE) in SLN. Methods: We retrospectively enrolled 107 female patients with cT1-T2 invasive BC and positive SLN biopsy. GP96 and AR expression were immunohistochemically evaluated on tissue microarrays constructed from two 2 mm diameter cores of formalin-fixed paraffin-embedded tumor tissues from each patient. ENE in SLN was measured in the highest (HD-ENE) and widest diameter (WD-ENE). Relative GP96 gene expression was determined using real-time quantitative PCR. Results: The analysis revealed ENE in SLN as the strongest predictive factor for non-SLN metastases. Patients with WD-ENE > HD-ENE had a higher risk of non-SLN metastases and worse DFS compared to those with WD-ENE ≤ HD-ENE. High GP96 expression was associated with a greater relative risk for locoregional recurrence but showed no significant impact on OS or DFS. Histological grade 3, extensive intraductal component (EIC), higher lymph node ratio (LNR), and negative AR were associated with worse DFS, while age, histological grade 3, EIC, and higher LNR were independent predictors of OS. GP96 mRNA levels were elevated in BC tissue compared to normal breast tissue. Conclusions: ENE in SLN is the strongest predictor of non-SLN involvement and could also have prognostic significance. While GP96 expression does not influence survival outcomes, AR expression could be used as a valuable biomarker in the follow-up of BC patients. Full article