Combined Chemoradiotherapy Research Articles

Honokiol Is More Potent than Magnolol in Reducing Head and Neck Cancer Cell Growth.

The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, like Magnolia-derived lignans-honokiol (HON) and magnolol (MAG)-can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics. The aim of this study was to evaluate the anti-cancer effects of HON and MAG in HNSCC cell lines and compare their effects between cisplatin-sensitive and cisplatin-tolerant cells. Cell viability was evaluated in FaDu and SCC-040 cells growing as monolayers and as spheroids. The effect of HON and MAG on the cell cycle, apoptosis, and gene expression was compared between wild-type FaDu cells and cisplatin persister FaDu cells. We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis. Thus, HON's and MAG's capacity to affect cisplatin persister cells needs further studies. In general, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D.

Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Mandibular Rhabdomyosarcoma in an Eniente Woman: About a Case

Introduction: Rhabdomyosarcoma is the most common soft tissue sarcoma in patients under 25 years of age. The occurrence of mandibular rhabdomyosarcoma in a pregnant woman is rare with an incidence of 0.07 to 0.1 and the literature describes one case per 1000 deliveries. Only biopsy and histological examination make a definitive diagnosis. Treatment is based on a combination of chemoradiation and surgery. Objectives: To describe the diagnostic and therapeutic aspects of mandibular rhabdomyosarcoma in pregnant women. Observation: It was a 19-year-old patient who had consulted for left mandibular swelling evolving over 28 weeks. A morphological assessment had been requested but being almost full-term, the patient chose to let her pregnancy progress. She was seen again after delivery with a swelling that had tripled in volume with abundant bleeding on the alteration of the general condition. The imaging concluded that there was a large osteolytic mass of the mandible. The biopsy performed came back in favor of an infiltrating pleomorphic rhabdomyosarcoma. Treatment consisted of radiation therapy followed by surgery. The evolution was marked by the death of the patient after 01 month of radiotherapy. Conclusion: Rhabdomyosarcoma is an aggressive malignant tumor that most often affects subjects under 25 years of age and its appearance in pregnant women is rare.

Management of patients with reduced dihydropyrimidine dehydrogenase activity receiving combined 5-fluoruracil-/capecitabine-based chemoradiotherapy.

5‑Fluoruracil (5-FU) and its oral prodrug capecitabine are mainstays in combined chemoradiotherapy regimens. They are metabolized by dihydropyrimidine dehydrogenase (DPYD). Pathogenic variants of the DPYD gene cause areduction in DPYD activity, leading to possibly severe toxicities. Therefore, patients receiving 5‑FU-/capecitabine-based chemoradiotherapy should be tested for DPYD variants. However, there are limited clinical data on treatment adjustments and tolerability in patients with decreased DPYP activity receiving combined chemoradiotherapy. Therefore, aretrospective analysis of the toxicity profiles of patients with decreased DPYD activity treated at our center was conducted. For all patients receiving 5‑FU-/capecitabine-based chemo(radio)therapy at our department, DPYD activity was routinely tested. Genotyping of four DPYD variants (DPYD*2A, DPYD*13, c.2846A > T, and haplotype B3) was conducted according to the recommendation of the German Society for Hematooncology (DGHO) using TaqMan hydrolysis polymerase chain reaction (PCR; QuantStudy3, Thermo FisherScientific, Darmstadt). DPYD variants and activity score as well as clinical data (tumor entity, treatment protocol, dose adjustments, and toxicity according to the Common Terminology Criteria for Adverse Events [CTCAE]) were assessed and reported. Of 261 tested patients, 21exhibited DPYD variants, 18of whom received chemoradiotherapy. All but one patient was treated for rectal or anal carcinoma. The observed rate of DPYD variants was 8.0%, and heterozygous haplotype B3 was the most common (5.75%). One patient exhibited ahomozygous DPYD variant. DPYD activity score was at least 0.5in heterozygous patients; chemotherapy dose was adjusted accordingly, with an applied dose of 50-75%. CTCAE grade2 skin toxicity (50%) and grade3 leukopenia (33.3%) were most common. One patient experienced atransient grade4 increase in transaminases. All high-grade toxicities were manageable with supportive treatment and transient. No CTCAE grade5 toxicities related to 5‑FU administration were observed. With dose reduction in heterozygous patients, toxicity was within the range of patients without DPYD variants. Our clinical data suggest that dose-adapted 5‑FU-/capecitabine-chemoradiotherapy regimens can be safely considered in patients with heterozygous clinically relevant DPYD variants, but that the optimal dosage still needs to be determined to avoid both increased toxicity and undertreatment in acurative setting.

524. SURVIVAL AFTER CURATIVELY INTENDED TREATMENT OF ESOPHAGEAL CANCER IN THE NORDIC COUNTRIES

Abstract Background Esophageal cancer is the 6th leading cause of cancer related death and has a high impact on life quality. With the ambition to improve long-term survival multimodal treatment including chemotherapy, or combined chemoradiotherapy, followed by surgical resection has become the standard of care. The overall aim of this study is to demonstrate the current treatment of esophageal cancer and survival in the Nordic countries. Methods In this cohort study based on prospective national patient registers all patients with esophageal cancer treated with curative intent between 2015-2020 in Sweden, Denmark, Norway, Finland and Island were included. Primary endpoint is 1-year survival after curative treatment for esophageal cancer. Secondary outcome is to describe curative intended treatment for esophageal cancer in the Nordic countries. Results The results will describe baseline characteristics, curative treatment including details of the surgical and perioperative treatment, and survival stratified by country. Conclusion The conclusion will describe the current curative treatment of esophageal cancer in the Nordic countries.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

The modified Surgical Apgar Score predictive value for postoperative complications after robotic surgery for rectal cancer.

The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients. The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100mL (IQR 80-130mL). We analyzed the association of postoperative complications with low mSAS. This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774-0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well. This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility.

Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.

Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients.

Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype. In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival. The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O6-methylguanine-DNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome. Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

What Does N2 Lymph Node Involvement Mean for Patients with Non-Small Cell Lung Cancer (NSCLC)?-A Review of Implications for Diagnosis and Treatment.

Patients with stage III NSCLC with N2 lymph node involvement carry a complex and diverse disease entity. Challenges persist in the areas of diagnosis, staging, multimodal management, and the determination of surgical indications and resectability criteria. Therefore, this review focuses on the latest updates in N2 disease staging and its prognostic and treatment implications. Emphasis is placed on the importance of accurate staging using imaging modalities such as [18F]FDG-PET/CT as well as minimally invasive mediastinal staging endoscopic techniques. The evolving role of surgery in the management of N2 disease is also explored. The benefits of neoadjuvant and adjuvant treatments have been demonstrated, along with the efficacy of a combined multimodal approach with chemo-immunotherapy in the perioperative setting, reigniting the debate of N2 disease subsets and optimal treatment options. Furthermore, this review addresses the controversies surrounding surgical approaches in upfront "borderline" resectable stage III NSCLC as well as the benefits of combined chemoradiotherapy with consolidation immunotherapy for patients with unresectable tumors. In conclusion, personalized diagnostic and treatment approaches tailored to individual patient characteristics, resource availability, and institutional expertise are essential for optimizing outcomes in patients with stage III-N2 NSCLC.

Dissociative Electron Attachment Dynamics of a Promising Cancer Drug Indicates Its Radiosensitizing Potential.

2-Bromo-1-(3,3-dinitroazetidin-1-yl)ethan-1-one (RRx-001) is a hypoxic cell chemotherapeutics with already demonstrated synergism in combined chemo-radiation therapy. The interaction of the compound with secondary low-energy electrons formed in large amounts during the physico-chemical phase of the irradiation may lead to these synergistic effects. The present study focuses on the first step of RRx-001 interaction with low-energy electrons in which a transient anion is formed and fragmented. Combination of two experiments allows us to disentangle the decay of the RRx-001 anion on different timescales. Sole presence of the electron initiates rapid dissociation of NO2 and HNO2 neutrals while NO2 - and Br- anions are produced both directly and via intermediate complexes. Based on our quantum chemical calculations, we propose that bidirectional state switching between π*(NO2) and σ*(C-Br) states explains the experimental spectra. The fast dynamics monitored will impact the condensed phase chemistry of the anion as well.

Analysis of high‑risk factors for brain metastasis and prognosis after prophylactic cranial irradiation in limited‑stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for brain metastases (BM). Limited-stage SCLC (LS-SCLC) can be effectively treated with chemoradiotherapy and prophylactic cranial irradiation (PCI) to enhance patient outcomes. The aim of the present study was to assess the risk factors and prognostic significance of brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) who attained complete remission (CR) or partial remission (PR) following combined chemoradiotherapy and subsequent prophylactic cranial irradiation (PCI). Data for 290 patients diagnosed with LS-SCLC and treated at Chengde Central Hospital and Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (Chengde, China), who achieved CR or PR and underwent PCI between 2015 and 2023, were retrospectively analyzed. BM rates and overall survival (OS) were estimated using the Kaplan-Meier method, whilst differences were assessed using the log-rank test. Risk factors affecting BM and OS were assessed using univariate and multivariate Cox regression analyses. The overall incidence of BM after PCI was 16.6% (48/290), with annual rates of 1.4, 6.6 and 12.8% at 1, 2 and 3 years, respectively. Multivariate Cox regression analysis identified an initial tumor size of >5 cm [hazard ratio (HR)=15.031; 95% confidence interval (CI): 5.610-40.270; P<0.001] as a significant independent risk factor for BM following PCI. The median OS was 28.8 months and the 5-year OS rate was 27.9%. The median OS for patients with and without BM at 27.55 and 32.5 months, respectively, and the corresponding 5-year OS rates were 8.3 and 31.8%, respectively (P=0.001). Median OS rates for stages I, II and III were 61.15, 48.5 and 28.4 months, respectively, with 5-year OS rates of 62.5, 47.1 and 21.6%, respectively (P<0.001). Further multivariate Cox regression analysis indicated that BM (HR=1.934; 95% CI: 1.358-2.764; P<0.001) and clinical stage (HR=1.741; 95% CI: 1.102-2.750; P=0.018; P=0.022) were significant independent risk factors associated with patient OS. In conclusion, a tumor size of >5 cm is a significant risk factor for BM following PCI in patients with LS-SCLS achieving CR or PR through radiotherapy and chemotherapy. Furthermore, BM and clinical staging independently influence OS.

Ewing's Sarcoma of Maxillary Sinus.

Ewing's sarcoma is a small round cell tumor commonly involving long bones. Head and neck involvement is seen less frequently with maxillary sinus being the rarest site. Here we report a case of a12-year-old female patient presented with left side facial swelling for 3 weeks duration which was diffuse and hard on palpation. CT and MRI of Nose & para nasal sinus revealed a mass lesion in the left maxillary sinus infiltrating and eroding the orbital wall and extending intracranially. Biopsy from the lesion revealed Ewing's sarcoma with strong positivity for CD-99 marker. Patient was referred to radiotherapy due to extensive disease at younger age. The CT and MRI along with HPE and IHC markers enables early diagnosis and prompt treatment that leads to better survival and prognosis, as unlike Ewing's sarcoma of long bones, that metastasize early. The combined chemoradiotherapy is now the standard line of treatment along with close follow up for at least 2 years.

CT Angiography-Guided Needle Insertion for Interstitial Brachytherapy in Locally Advanced Cervical Cancer.

CT angiography might be a suitable procedure to avoid arterial puncture in combined intracavitary and interstitial brachytherapy for cervical cancer curatively treated with combined chemoradiation and brachytherapy boost. Data in the literature about this technique are scarce. We introduced this method and collected brachytherapy data from patients treated in our department between May 2021 and April 2024. We analyzed the applicator subtype, needle insertion (planned versus implanted), implanted depth and the role of CT angiography in selecting needle trajectories and insertion depths. None of the patients managed through this protocol experienced atrial puncture and consequent hemorrhage. Needle positions were accurately selected with the aid of CT angiography with proper coverage of brachytherapy targets and avoidance of organs at risk. CT angiography is a promising method for guiding needle insertion during interstitial brachytherapy.

Clinical diagnosis and treatment of 37 cases of gallbladder neuroendocrine carcinoma

ObjectiveThis study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).MethodsRetrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis.ResultsTwelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004).ConclusionSurgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.

A prospective multicenter trial of dose escalation for weekly gemcitabine concurrent with intensity-modulated radiotherapy following cisplatin and gemcitabine induction chemotherapy in patients with locally advanced nasopharyngeal carcinoma.

6071 Background: Gemcitabine and cisplatin induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy, constitutes the standard treatment for locally advanced nasopharyngeal carcinoma (LANPC). However, the substantial cumulative dosage of cisplatin used in this approach renders it intolerable for many patients due to advanced age or compromised renal function. Therefore, identifying alternative chemotherapeutic agents is crucial. Gemcitabine is a potent radiosensitizer with an overall favorable safety profile. Despite extensive research on the maximum tolerated dose (MTD) of concurrent gemcitabine chemotherapy in head and neck cancer, its MTD as a single-agent chemotherapy concurrently administered with intensity-modulated radiotherapy (IMRT) in LANPC remains uncertain. Methods: Patients diagnosed with stage III-IVa nasopharyngeal carcinoma were prospectively enrolled in three hospitals located within the largest NPC endemic area in southern China. After two cycles of cisplatin plus gemcitabine induction chemotherapy, patients underwent combined concurrent radiochemotherapy (70 Gy/6-7 weeks) with weekly gemcitabine. The initial dose level was set at 25mg/m2 and subsequently escalated in a sequential manner to higher doses of 50mg/m2, 100mg/m2, 200mg/m2, and 300mg/m2 etc. Our study employed a dose escalation strategy in which the dosage was incremented to the next group only if no more than one out of six patients experienced Dose-Limiting Toxicity (DLT), until DLT occurred in at least two patients. Patients underwent follow-up evaluations every three months. This study is registered with ClinicalTrials.gov under NCT04522050. Results: Between October 2018 and December 2023, a total of 39 Chinese patients were enrolled, 36 (27 males, 9 females) patients were considered evaluable. The incidence of DLT was observed in two out of six patients receiving a dosage level of 300 mg/m², with both cases presenting Grade 3 oral mucositis. Subsequently, the study was replicated using the same dosage level, resulting again in two instances of DLT: one case with Grade 3 radiation dermatitis and another case with oral mucositis. Consequently, a reduced dosage level of 200mg/m² was determined as MTD. No significant hematological toxicity or serious gastrointestinal adverse events were observed. Tumor response evaluation by MRI after twelve weeks of IMRT showed a complete response rate of 100%. To date, only two cases (5.56%) have been reported exhibiting tumor recurrence. Conclusions: The MTD for weekly gemcitabine with IMRT following induction chemotherapy in LANPC is determined to be 200 mg/m2. The DLT associated with this treatment regimen primarily consists of radiation dermatitis and/or oral mucositis. Clinical trial information: NCT04522050 .

Chemotherapy with or without surgery for locally advanced or borderline resectable pancreatic ductal adenocarcinoma: A retrospective multicenter international study.

e16352 Background: Current clinical guidelines recommend surgery for patients with locally advanced (LA)/borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) who achieve disease control after induction therapy. However, the additional survival benefit of surgery in these patients is unknown. Methods: In this multicenter international retrospective cohort study, consecutive patients with BR/LA PDAC who achieved disease control after three to six months of induction therapy (combination chemotherapy or chemoradiotherapy) between January 2014 and July 2021 were retrospectively identified at 8 centers in Germany and Italy. Resectability status was determined by consensus in a multidisciplinary tumor board based on imaging findings, serum CA19-9, performance status and clinical response. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to compare survival data. Results: A total of 138 patients who achieved disease control with induction therapy were analyzed. The median age at diagnosis was 66 years (range 45-82) and 43% of patients were female. 73 patients underwent surgery and 65 patients did not (median age 64 and 69 years, respectively, p = 0.02). Median OS was 20.0 months (95%CI 16.1-23.8) in the surgery group and 18.0 months (95%CI 13.6-22.4) in the nonsurgery group (hazard ratio for death, 0.90; 95%CI, 0.63 to 1.29, p = 0.57). Median PFS was 14.0 months (95%CI 8.9-19.1) in the surgery group and 15.0 months (95%CI 11.7-18.3) in the nonsurgery group (hazard ratio for disease progression, 1.04; 95%CI, 73 to 1,47, p = 0.83). The 2-year survival rates in the surgery and nonsurgery groups were 32.9% and 40.0%, respectively, with an overall odds ratio of 0.74 (95% CI: 0.37-1.47). Conclusions: In our multicenter international retrospective analysis, additional surgery did not confer a survival advantage to patients with BR/LA PDAC who achieved disease control with induction therapy.

Efficacy and safety of combined anti-angiogenic chemoradiotherapy with PD-1 monoclonal antibody in advanced melanoma: A retrospective study.

e21516 Background: Malignant melanoma, characterized by its aggressiveness and early metastasis, poses significant challenges in terms of treatment efficacy. This retrospective study aimed to assess the efficacy and safety of the integrated treatment regimen in patients (pts) with advanced melanoma. Methods: 42 pts with histologically confirmed inoperable stage III or IV melanoma and ECOG PS 0 or 1 were included in this retrospective study conducted from September 2020 to August 2023. Pts received combination therapy with albumin-bound paclitaxel, bevacizumab (bev), and toripalimab (tor) (Q3W). Maintenance therapy with bev and tor was given after 6-8 cycles without disease progression or intolerable adverse reactions. Personalized radiotherapy was delivered. Radiological evaluations were performed every 2 cycles during combination therapy and every 3 cycles during maintenance therapy using RECIST 1.1 criteria. Adverse events were graded according to NCI-CTCAE version 4.03. Results: All pts underwent at least one efficacy evaluation. The male-to-female ratio was 1:1, with a median age of 61.5 years (range: 34-80 years). Treatment-naïve pts accounted for 47.6% (n = 20), second-line pts for 35.7% (n = 15), third-line pts for 11.9% (n = 5), and fourth-line pts for 4.8% (n = 2). There were 25 cases (59.5%) of acral melanoma, 4 cases (9.5%) of cutaneous melanoma, 12 cases (28.6%) of mucosal melanoma, and 1 case (2.4%) with an unknown primary site. During the treatment period, 66.7% (n = 28) of pts received radiotherapy. As of December 2023, 26 out of 43 pts showed tumor shrinkage, including 2.4% (n = 1) achieving CR through conversion surgery following PR, maintaining it for 30 months. The ORR was 61.9%, with a confirmed ORR of 57.1%, and a DCR) of 92.9%. The median PFS was 14.4 months, and the median OS has not yet been attained. Common adverse events included alopecia (100%), hypertriglyceridemia (61.9%), elevated transaminases (59.5%), anemia (59.5%), leukopenia (52.4%), hypercholesterolemia (52.4%), peripheral neuropathy (50%). No treatment-related deaths were reported. Conclusions: This study demonstrates that PD-1 monoclonal antibody in combination with chemotherapy, anti-angiogenic therapy and radiotherapy offers a promising therapeutic option for advanced melanoma. Keywords:Malignant melanoma; Albumin-bound paclitaxel; Bevacizumab; PD-1 monoclonal antibody; Radiotherapy.

Prognostic nomogram, demographics and comparative analysis of prostate small cell and large cell neuroendocrine carcinoma.

e17010 Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences from common types of prostate cancer. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was found to be 71.5 years and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasians (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients of stage 3 tumors, as well as patients who underwent surgery and radiation. The nomogram also indicated a slight increase in mortality with tumors of greater size. Conclusions: Small-cell and large-cell neuroendocrine carcinomas of the prostate are rare; their aggressive nature calls for a deeper understanding and improved prognostic tools. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging arena of oncology.

Endoscopic surgery combined chemoradiotherapy and PD-1 blockade in patients with sinonasal mucosal melanoma.

e21552 Background: Primary sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease different from cutaneous melanoma. The best treatment modality including the role of immune checkpoint blockade in SNMM has not been defined. Methods: Between 2021 and 2023, patients with previously untreated sinonasal melanoma were enrolled by three single-center investigator-initiated phase II clinical trials (ChiCTR2100046498 / ChiCTR2100045797/ ChiCTR2100049031). Eligible patients in ChiCTR2100045797 trial received postoperative radical chemoradiotherapy combined with toripalimab (a PD-1 inhibitor) for a year or until the disease progressed. Eligible participants in ChiCTR2100046498 study received surgery combined with radiation without immunotherapy. And for patients in ChiCTR2100049031 study, preoperative radiation was carried out firstly. The locoregional control, distant metastasis-free survival (DMFS), and overall survival (OS) were the main efficacy goals. Results: Fifty-four patients were enrolled (mean age 62 years, 33 males [61.1%] and 21 women [38.9%]) with 2y-OS rate 62.3±7.9%, 2y-RFS rate 67.1±8.2%, and 2y-DMFS rate 63.9±8.1%. Patients with T3 (n = 23), T4a (n = 14), and T4b (n = 17) stages, including12 patients with node-positive disease, were included at baseline. During a median follow-up of 11 months, 19 patients ultimately died, 10 experienced relapses, and 17 developed metastases. Tumor T staging was demonstrated to be an independent prognostic predictor according to the Cox univariate analysis. The primary factor contributing to a poor prognosis and the primary cause of death for 73.7% of patients was distant metastases. Preoperative radiation had an improved long-term survival with 2y-OS rate of 85.7±13.2%, and it can considerably lower the risk of distant metastases (p≤0.05). The overall survival rate for patients receiving postoperative chemoradiotherapy combined with immunotherapy was higher than that for patients not receiving immunotherapy (2y-OS rate 74.1±11.4% vs. 39.3±15.8%), although the difference was not statistically significant due to a small number of patients (p = 0.16). No immune-related adverse effects grade≥3 was recorded. Conclusions: The primary cause of the poor prognostic performance of SNMM is distant metastasis. The risk of distant metastases might be considerably decreased by preoperative radiation treatment. Surgery combined with radiation and immunotherapy could bring promising survival benefit. The way forward may involve investigating the combination of immunotherapy and preoperative radiotherapy. Clinical trial information: NCT04879654 ; NCT05009446 .