Search Results (64)

The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%. Full article

Purpose: We aimed to identify the impact of conversion surgery to survival in patients with stage IV esophageal cancer who have a stabilized disease and good treatment response before surgery. Patients and Methods: This retrospective study included patients with esophageal cancer M1 disease treated at a tertiary medical center from April 2002 to June 2021. For patients with a good clinical response to chemoradiation and well-controlled metastatic lesions, esophagectomy and lymphadenectomy were performed. A propensity score-matching (PSM) study with a 1:2 ratio and based on patient age, tumor stage, and metastasis status was conducted for verifying the results. Results: We enrolled 162 patients, including 124 treated with concurrent chemoradiation therapy (CCRT) alone and 38 treated with CCRT followed by esophagectomy. A total of 114 patients were analyzed using PSM, including 76 patients treated with CCRT alone and 38 patients treated with CCRT and surgery. The 3- and 5-year OS was 24.6% vs. 2.8% and 12.3% vs. 1.4% (p = 0.006), and PSM was 24.6% vs. 4.6% and 12.3% vs. 2.3% (p = 0.033) for those with or without esophagectomy, respectively. Multivariate analysis revealed surgery with esophagectomy as an independent prognostic factor for OS with odd ratios (95% confidence interval [CI]) of 1.91 (1.23–2.95) (p = 0.004). Conclusions: Surgical resection following CCRT holds a potential survival benefit for the patients with a favorable response to CCRT for patients with stage IV esophageal cancer. Full article

Background and Objectives: We aimed to investigate the treatment outcomes and prognostic factors of survival among patients with glioblastoma who underwent 6-week concurrent chemoradiation therapy (CCRT) followed by temozolomide (TMZ) with Stupp’s regimen in a single tertiary institution. Materials and Methods: Eighty patients with glioblastoma who underwent 6-week CCRT followed by TMZ between June 2010 and January 2024 were retrospectively investigated. A survival analysis was performed of factors such as age, O (6)-methylguanine-DNA methyltransferase promoter (MGMT) methylation, extent of resection, pre- and post-operative Karnofsky Performance Status, and inflammatory markers such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio. Post-operative inflammatory markers were assessed at 2–3 weeks post-operative before the initiation of CCRT. A subgroup analysis was performed of patients who underwent non-gross total resection (GTR). Results: The median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 8.97 months and 19.0 months, respectively. Older age (≥65 years) and non-GTR status were adverse prognostic factors of PFS and OS. MGMT methylation is a favorable prognostic factor for PFS and OS. In the subgroup of patients who underwent non-GTR, MGMT methylation and post-operative LMR (<3.2/>3.2) were independent prognostic factors for PFS and OS. Conclusions: As with previous studies, older age, MGMT methylation, and extent of resection were independent prognostic factors for the survival of patients with glioblastoma who underwent standard treatment with Stupp’s regimen. MGMT methylation and post-operative LMR were significant prognostic factors for PFS and OS among patients who underwent non-GTR. The prognostic significance of post-operative inflammatory markers for treatment response and survival should be further validated in glioblastoma patients treated with Stupp’s regimen. 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

Background/Objectives: Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy (NACT + CCRT) and adjuvant chemotherapy following CCRT (CCRT + ACT) have inconsistent effects on the survival of women with locally advanced cervical cancer (LACC) compared to CCRT. Moreover, the effects of NACT + CCRT and CCRT + ACT have not been clearly compared. This study compared the effects of NACT + CCRT and CCRT + ACT on survival using a network meta-analysis to select the optimal treatment in women with LACC. Methods: The PubMed, Medline, and Embase databases were searched, and six randomized controlled trials assessing the progression-free survival (PFS) and overall survival (OS) in women with newly diagnosed LACC treated with NACT + CCRT, CCRT + ACT, or CCRT alone (controls) were identified. A network meta-analysis was conducted. Results: Indirect comparisons showed no significant differences in PFS and OS between NACT + CCRT and CCRT + ACT. Direct comparisons also showed similar PFS and OS between NACT + CCRT and CCRT and between CCRT + ACT and CCRT. CCRT + ACT exhibited the highest surface under the cumulative ranking curve (SUCRA) value as a better treatment option for the PFS and OS (CCRT + ACT vs. NACT + CCRT vs. CCRT: 72% vs. 26.8% vs. 51.2% in PFS and 64.3% vs. 45.1% vs. 40.7% in OS). Conclusions: In women with LACC, NACT + CCRT had no different effects on the PFS and OS compared to CCRT + ACT, despite the relatively higher SUCRA value observed for CCRT + ACT. Further studies are warranted to clarify the effects of these strategies. Full article

Background: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm³) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well. Full article

The addition of durvalumab consolidation to concurrent chemoradiation therapy (cCRT) has fundamentally changed the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Nevertheless, concerns related to esophagitis and pneumonitis potentially impact the broad application of all regimen components. A Canadian expert working group (EWG) was convened to provide guidance to healthcare professionals (HCPs) managing these adverse events (AEs) and to help optimize the patient experience. Integrating literature review findings and real-world clinical experience, the EWG used a modified Delphi process to develop 12 clinical questions, 30 recommendations, and a risk-stratification guide. The recommendations address risk factors associated with developing esophagitis and pneumonitis, approaches to risk mitigation and optimal management, and considerations related to initiation and re-initiation of durvalumab consolidation therapy. For both AEs, the EWG emphasized the importance of upfront risk assessment to inform the treatment approach, integration of preventative measures, and prompt initiation of suitable therapy in alignment with AE grade. The EWG also underscored the need for timely, effective communication between multidisciplinary team members and clarity on responsibilities. These recommendations will help support HCP decision-making related to esophagitis and pneumonitis arising from cCRT ± durvalumab and improve outcomes for patients with unresectable stage III NSCLC. Full article

Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include maximal debulking transurethral resection of bladder tumor (TURBT), concurrent chemoradiation therapy, followed by cystoscopy to assess response. At this time, maximal TURBT is recommended for patients prior to the initiation of chemoradiation therapy or in patients with residual bladder tumors after the completion of chemoradiation therapy. That being said, TURBT carries significant risks such as bladder perforation, bleeding, and infection, ultimately risking delayed systemic treatment. Hence, understanding its role within trimodal therapy is crucial to avoid undue suffering in patients. Herein, we review the current literature on the impact of debulking TURBT in non-metastatic MIBC. Full article

Background: Lymphadenectomy plays a crucial role in the surgical management of early- stage esophageal cancer. However, few studies have examined lymphadenectomy outcomes in advanced stages, particularly in patients who initially underwent concurrent chemoradiation therapy. This retrospective study investigates the effect of lymphadenectomy in patients diagnosed with AJCC 8th-edition clinical stage III esophageal squamous cell carcinoma who received concurrent preoperative chemoradiation. Methods: Data from 1994 to 2023 were retrieved from our retrospective database. All patients underwent a uniform evaluation and treatment protocol, including preoperative concurrent chemoradiation therapy comprising cisplatin and 5-fluorouracil, followed by esophagectomy. The analysis encompassed clinical T and N stages, tumor location, tumor grade, pathological T and N stages, pathological stage, and the extent of lymph node dissection. Overall survival, “Free-To-Recurrence”, and disease-free survival were assessed via Kaplan–Meier survival curves and the Cox regression model for multivariate analysis. Results: The dataset was stratified into two groups according to extent of lymph node dissection, with one group having <15 dissected nodes and the other having ≥15 dissected nodes. The group with <15 nodes exhibited a shorter “Free-To-Recurrence”, worse disease-free survival, and lower overall survival. In multiple-variate analysis (Cox regression model), the number of dissected lymph nodes emerged as a significant factor influencing overall survival and freedom from recurrence. Conclusions: The quantity of lymphadenectomy is a crucial determinant for patients with AJCC 8th-edition clinical stage III esophageal squamous cell carcinoma receiving preoperative concurrent chemoradiation. Full article

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m²) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits. Full article

Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages. Full article

Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management. Full article

Dedifferentiation is a very rare phenomenon in uterine leiomyosarcoma (LMS). The aim of this study was to comprehensively analyze the clinicopathological characteristics of uterine dedifferentiated LMS (DDLMS). We reviewed electronic medical records and pathology slides from five patients with uterine DDLMS and performed immunostaining. The mean age of the patients was 56 years. Two patients presented with abdominal discomfort, while in three cases the uterine tumors were detected on routine medical examination. The mean size of the tumors was 17.0 cm. Four patients underwent hysterectomy. The initial stages were distributed as IB (2/5), IIIC (2/5), and IVC (1/5). Post-operative concurrent chemoradiation therapy, radiation therapy, and chemotherapy were administered in one, one, and two patients, respectively. Despite post-operative treatment, three patients developed metastatic recurrences in the abdominal and pelvic organs. Recurrence-free survival time ranged between 4 and 30 months. Histologically, the differentiated areas demonstrated the classic morphology of malignant smooth muscle differentiation, whereas the dedifferentiated areas resembled undifferentiated pleomorphic sarcoma and were characterized by large pleomorphic tumor cells admixed with haphazardly arranged atypical cells with marked nuclear pleomorphism. All cases also exhibited heterologous components, including chondrosarcoma (CSA; 3/5) and rhabdomyosarcoma (2/5). In two cases, the heterologous components were initially detected in primary tumors. In three cases, the primary tumors did not exhibit any dedifferentiated or heterologous components. Instead, more than half of the recurrent tumors consisted of heterologous components. Three cases showed a sharp demarcation between the LMS and CSA components, while in two cases the dedifferentiated area imperceptibly merged with the differentiated component. Immunostaining revealed that the dedifferentiated components exhibited a lack of desmin immunoreactivity in three of the four examined cases. A subset of uterine LMS represents various amounts and types of dedifferentiation and heterologous components in both primary and recurrent tumors. Routine recognition of DDLMS and distinction from its mimickers are required for accurate diagnosis and further characterization of these rare tumors. Full article

Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m² twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest. Full article

Background: Stage III nonsmall cell lung cancer (NSCLC) represents a heterogeneous group of patients. Many patients are treated with curative intent multimodality therapy, either surgical resection plus systemic therapy or chemoradiation plus immunotherapy. However, many patients are not suitable for curative intent therapy and are treated with palliative systemic therapy or best supportive care. Methods: This paper is a review of recent advances in the management of patients with curative intent disease. Results: There have been significant advances in curative intent therapy for patients with stage III NSCLC in recent years. These include both adjuvant and neoadjuvant systemic therapies. For patients with resectable NSCLC, two trials have demonstrated that adjuvant atezolizumab or pembrolizumab, following chemotherapy, significantly improved disease-free survival (DFS). In patients with tumours harbouring a common mutation of the EGFR gene, adjuvant osimertinib therapy was associated with a large improvement in both DFS and overall survival (OS). Five randomized trials have evaluated chemotherapy plus nivolumab, pembrolizumab, durvalumab, or toripalimab, either as neoadjuvant or perioperative (neoadjuvant plus adjuvant) therapy. All five trials show significant improvements in the rate of pathologic complete response (pCR) and event-free survival (EFS). OS data are currently immature. This would now be considered the standard of care for resectable stage III NSCLC. The addition of durvalumab to chemoradiation has also become the standard of care in unresectable stage III NSCLC. One year of consolidation durvalumab following concurrent chemoradiation has demonstrated significant improvements in both progression-free and overall survival. Conclusions: Immune checkpoint inhibitor (ICI) therapy has become a standard recommendation in curative intent therapy for stage III NSCLC. Full article