Stage IVA Patients Research Articles

Comparative Analysis of Concurrent Chemoradiotherapy Versus Chemotherapy Alone as First-Line Palliative Treatments for Advanced Esophageal Squamous Cell Carcinoma

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan–Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43–0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29–0.93]), but not in stage IVB patients (HR: 0.76 [0.51–1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35–0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status.

Prognostic Value and Clinical Implication of Lymph Node-to-Primary Tumor SUV Ratio in Node-Positive Hypopharyngeal Squamous Cell Carcinoma Treated With Radiotherapy With or Without Chemotherapy.

The aim of this was to evaluate the prognostic significance of the nodal-to-primary tumor SUVmax ratio (NTR) in patients with node-positive hypopharyngeal squamous cell carcinoma (HPSCC) treated with radiotherapy with or without concurrent chemotherapy. The study aims to enhance prognostic accuracy by incorporating NTR into the American Joint Committee on Cancer (AJCC) staging system. This retrospective study included 191 patients with biopsy-proven node-positive HPSCC treated from 2005 to 2013. NTR was calculated as the ratio of SUVmax of metastatic lymph nodes to the primary tumor's SUVmax. Survival analyses were conducted using Cox regression models and Kaplan-Meier analysis. Receiver operating characteristic analysis compared the prognostic performance of the modified and AJCC staging systems. The median follow-up was 8.27 years, with 135 deaths (70.7%). High NTR (≥0.63) was significantly associated with worse overall survival (OS) and was an independent prognostic factor in multivariable analysis (adjusted hazards ratio [HR] = 1.63, P = 0.007). Median OS for high NTR was 17.4 months, compared with 75.2 months for low NTR. High NTR significantly predicted worse OS within AJCC stage IVA patients (HR = 6.09, P = 0.014). Patients in modified stage IVA (AJCC stage IVA with low NTR) had significantly longer OS than those in modified stage IVB (AJCC stage IVA with high NTR and AJCC stage IVB) (HR = 8.62, P = 0.003). The modified staging system incorporating NTR showed superior prognostic performance compared with the AJCC staging system. NTR is a significant independent prognostic factor for OS in node-positive HPSCC patients. Integrating NTR into the AJCC staging system improves prognostic accuracy.

EGFR-Tyrosine Kinase Inhibitor Combined with Radiotherapy in 105 Patients of Lung Adenocarcinoma with Brain Metastasis: A Retrospective Study of Prognostic Factor Analysis

Introduction: This study aimed to retrospectively analyse the response and prognosis factors for patients with lung adenocarcinoma exhibiting brain metastasis and epidermal growth factor receptor (EGFR) mutations, who were treated with a combination of EGFR-tyrosine kinase inhibitor (TKI) and brain radiotherapy (RT). Methods: Clinicopathological data of patients with lung adenocarcinoma were collected from January 2021 to January 2024 at the First Affiliated Hospital of Hebei North University. Statistical analysis was performed using SPSS version 26.0, with significance set at p < 0.05. Results: A total of 105 patients were included. The overall survival (OS) rates at 1, 2, and 3 years were 82.9%, 61.2%, and 33.7%, respectively. The progression-free survival 1 (PFS1) rates at 1, 2, and 3 years were 62.7%, 36.6%, and 22.1%, respectively. The progression-free survival 2 (PFS2) rates at 1, 2, and 3 years were 80.8%, 54.6%, and 31.4%, respectively. The median OS, PFS1, and PFS2 were 29.8, 18.0, and 28.1 months, respectively. Cox multivariate analysis identified gene mutation status and brain radiation dose as independent prognostic factors for OS. For PFS1, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors. Clinical stage, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors for PFS2. Conclusion: The combination of TKIs and brain RT is effective for patients with lung adenocarcinoma with EGFR mutations and brain metastases. Patients with exon 19 Del or exon 21 L858R mutations and brain radiation doses ≥40 Gy exhibit longer OS, PFS1, and PFS2. Additionally, complete remission + partial remission is associated with extended PFS1 and PFS2, while patients in stage IVA show longer PFS2.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial)

ObjectiveThis study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial).MethodsIn a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared.ResultsAmong 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3–4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively.ConclusionsCombining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Stratified Prognostic Comparison Between Stage IIB-IVA Cervical Adenocarcinoma and Squamous Cell Carcinoma: A SEER Database-Based Study.

In current most observational studies, the prognosis of cervical adenocarcinoma is worse than that of cervical squamous cell carcinoma. However, most of the current studies are holistic and lack more detailed staging and grouping analysis of the prognosis of the two types of cervical tumors. Inclusion from the SEER database of stage IIB-IVA cervical squamous cell carcinoma and cervical adenocarcinoma patients who did not undergo surgery from 2000 to 2019, underwent radiotherapy/chemotherapy/radiotherapy and chemotherapy/no treatment, and then propensity score matching (PSM) was performed to eliminate confounding factors between cervical squamous cell carcinoma and cervical adenocarcinoma patients with the same stage and treatment method. After matching the original data and propensity score, logarithmic rank test and chi square test were used to evaluate the survival benefits of different stages and treatment methods for patients using Kaplan Meier curve. The prognosis of two types of cervical tumors under the same treatment method was compared, and factors that may cause poor prognosis were analyzed, excluding confounding factors. A total of 10,057 patients were included in this study, and survival analysis showed a significant correlation between the treatment method used and patient prognosis (P<0.05). However, for patients who received radiotherapy or no special treatment, OS and CSS were only related to tumor stage and not to tumor type. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients are not related to tumor pathological characteristics, while the OS of stage IIB patients is not related to tumor properties after PSM. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients were not related to histological type, while the OS of stage IIB patients was not related to histological type after PSM.

Effect of waiting time for radiotherapy after last induction chemotherapy on prognosis of locally advanced nasopharyngeal carcinoma.

The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003-1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57-4.6), OS (HR = 2.55; 95%CI: 1.29-5.03), DMFS (HR = 3.07; 95%CI: 1.64-5.76) and LRFS (HR = 2.26; 95%CI: 1.21-4.21). The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.

Efficacy and Safety of Modified BV-AVD-R Regimen in Chinese Children with Previously Untreated Intermediate- and High-Risk Classical Hodgkin's Lymphoma: An Open Label, Non-Randomized, Single-Arm, Phase 2 Study from Single Center

Introduction Classical Hodgkin lymphoma (cHL) accounts for about 4.8% of childhood malignant neoplasm, and the incidence of cHL in Chinese children and adolescents (0-19 years old) is about 1.78/million, which is a group of relatively low malignancy and curable tumor. With the prolonged survival of children and adolescents with cHL, the incidence of muscle and skeletal malformations, lung and cardiovascular diseases, infertility and secondary tumors increased significantly during long-term follow-up. Therefore, the goal of childhood cHL treatment is to achieve and maintain the high efficacy while reduce the treatment-related complications. Brentuximab vedotin (BV), an antibody-drug conjugates (ADC) targeting CD30, has been evaluated well in American children and some regions, but no clinical studies to explore the efficacy and safety of BV in Chinese children with cHL. Therefore, the objective of our study is to evaluate the efficacy (objective response rate, including CR and PR) and safety (short - and long-term safety) of modified BV-AVD-R regimen (Brentuximab vedotin + Rituximab + Doxorubicin + Vinblastine + Dacarbazine) in Chinese children with previously untreated intermediate- and high-risk classical HL. Methods This study is a prospective study with period from October 2022 to December 2024, and planned to enroll 44 children with newly diagnosed intermediate- and high-risk classical HL. All patients will undergo PET/CT at the time of initial diagnosis and after 2 cycles of modified BV+R+AVD regimen to determine early response. Rapid early responders (RER) defined as CR after 2 cycles of therapy. Slow early responders (SER) defined as no CR (partial response (PR) or stable disease) after 2 cycles of therapy. Intermediate-risk patients were stage IA bulk/E, IB, IIA bulk/E, IIB, and IIIA. High-risk patients were stage IIB bulk/E, IIIA bulk/E, IIIB, and IVA/B(Figure 1). The primary endpoints include ORR (CR+PR) and adverse events. The secondary endpoints include progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year. Results From October 2022 to July 2023, a total of 14 children with newly diagnosed classical HL were enrolled, and 12 patients who had completed at least 2 cycles treatment were eligible for evaluation. 9 boys and 3 girls were enrolled, with median age of 10 years (range 7-15 years). Risk group: 9 patients in high-risk group, 3 patients in intermediate-risk group; Clinical stage: 5 patients in stage IIIA, 2 patients in stage IIIB, 4 patients in stage IVA, and 1 patient in stage IVB. Pathologic subtype: 7 patients of nodular sclerosis type and 5 patients of mixed cell type. Treatment: A total of 33 cycles of modified BV+R+AVD regimen were completed, with 66 doses of BV. The median number of treatment cycles was 3 cycles (range 2-6). 11 patients achieved CR and 1 patient achieved PR after 2 cycles, and the ORR was 100% (12/12). As of July 28, 2023, 4 children had stopped follow-up and achieved CR without sequential radiotherapy. The median follow-up was 6 months (range 2-10). 12 patients successfully received and completed BV infusions, mild nausea and vomiting (10/12), alopecia (9/12) and sensory abnormalities (3/12) were observed. Serious adverse events were mainly grade ≥3 blood cell abnormalities (10/12), none of which had an impact on the treatment flow. No patient withdrew from the study, indicating good adherence to the regimen. Conclusion The risk-adapted modified BV+R+AVD regimen for newly diagnosed Chinese children and adolescents with classical HL showed favorable treatment outcomes with good early response rate and sustained response rate. The regimen could also reduce sequential radiotherapy and demonstrated well safety and tolerability. The study is still ongoing.

Toripalimab Combined with Chemoradiotherapy for Locally Advanced Cervical Squamous Cell Carcinoma Patients: Early Results of Safety and Feasibility

To assess the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. Twenty-two locally advanced cervical cancer patients, regardless of programmed death ligand-1 (PD-L1) status, received toripalimab treatment combined with concurrent chemoradiotherapy (CCRT), includes cisplatin (40 mg/m2, once a week for 5 weeks), radiotherapy (45-50.4 Gy/25-28Fx, 5 fractions a week, followed by brachytherapy 24-30 Gy/3-5Fx) and toripalimab (240mg on day 1, 22 and 43). The primary endpoints were safety and 2-year progression-free survival (PFS). The median age was 55 years old (42 to 72), with 2 patients in FIGO stage Ⅱ, 15 patients in stage ⅢC, and 5 patients in stage ⅣA. All patients completed CCRT successfully. Grade Ⅲ and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient had a grade Ⅴ AE. The most frequent grade Ⅲ AE was leukopenia (8/22, 36.4%). The most common immunotherapy-related adverse event was hypothyroidism (2/22, 9.1%). The objective response rate (ORR) was 100%. At data cutoff (Sep 30, 2022), the median follow-up was 19.7 months (7.67 to 26.1 months). The LC and the PFS rate were 95.5% and 81.8%, and the OS rate was 90.9%. The patients with baseline absolute lymphocyte count (ALC) ≤1.255 × 10^9/L had significant higher rates of metastasis than those with ALC >1.255 × 10^9/L (42.9% vs 0%, p = 0.023). Toripalimab combined with CCRT achieved good tolerance and demonstrated promising anti-tumor effects in patients with locally advanced cervical cancer. Longer follow-up results and further phase Ⅱ/Ⅲ studies are expected. Chinese Clinical Trial Registry number, ChiCTR2000032879.

Cervical Cancer Progression in Patients Waiting for Radiotherapy Treatment at a Referral Center in Ethiopia: A Longitudinal Study

ABSTRACT Nonmetastatic cervical cancer is a highly curable malignancy, and radiotherapy (RT) remains the mainstay treatment. Early initiation is critical, and the optimal time to initiate RT for cure is 6 weeks, with a reported 15% decrease in 3-year overall survival for those who wait 40 days. There is considerable variation in the waiting time to initiate RT between countries, with a median time of 27.2 days in Ontario, Canada and 108 days in South Africa. Real-world evidence of cancer progression because of treatment delay is scarce in low-income countries. Ethiopia, a country of 120 million, had a single machine at Tikur Anbessa Specialized Hospital (TASH) until it acquired a linear accelerator very recently. This study aimed to assess the extent of delay in receiving RT and the effect of delay on the natural disease court in patients with cervical cancer treated at TASH. This study was conducted at TASH between January 2019 and May 2020 and evaluated patients at different time points before and after RT. All individuals who were diagnosed with cervical cancer (stage IIB to stage IVA) and booked for RT at TASH were included. Concurrent chemoradiotherapy was administered for cervical cancer with weekly cisplatin as a chemotherapy agent. A total of 115 patients were included in this study. The median time between pathologic diagnosis and booking RT was 19 days, and the median time from booking to RT initiation was 458 days. The total median time from diagnosis to treatment was 477 days, and the median time to disease progression was 51 days. During the waiting period for RT, the stage was reassessed for 105 patients. The number of patients in stage IIB, IIA, and IIIB decreased during this period, whereas the number of patients in stage IVA increased from 20 (17.4%) to 30 (26.1%), 2 (1.8%) developed distant metastasis to the lungs (stage IVB), and 37 died before receiving a phone call for RT. Of 115 patients booked to receive CCRT, only 9 (7.8%) received CCRT, 80 (69.9%) received a single shot of palliative RT due to disease progression, and 25 (21.7%) did not receive RT at all. The mean and median survival times were 20.1 months (95% confidence interval [CI], 18.3–22.7) and 21 months (95% CI, 18.3–23.8), respectively. Waiting time, stage at presentation, distant metastasis during the waiting time, hydronephrosis during the waiting time, and type of treatment were significantly associated with survival. Multivariate cox regression using these variables found that patients with stage IIIB were 2.2 times more likely to die than those with stage IIB (adjusted hazards ratio, 2.2; 95% CI, 1.07–4.48), and patients with stage IVA were 20.95 times more likely to die than patients with stage IIB (adjusted hazards ratio, 20.95; 95% CI, 6.26–70.03). Prolonged waiting time increased the mortality rate of cervical cancer by 2.9 (95% CI, 1.07–4.5). This study provides a significant advancement in our understanding of cervical cancer care in low-income countries. The median waiting time diagnosis to treatment was 477 days, whereas the median waiting period for disease progression was 51 days, resulting in unnecessary disease progression, change in treatment intent from curative to palliative, and increased mortality. These findings highlight the need to increase access to RT services in lower-income nations to reduce wait times and provide better cancer care.

Efficacy of hypofractionated preoperative chemoradiotherapy in rectal cancer.

The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4-8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits.

Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

AIM: This study aims to determine the relationship between the HPV genotype in uterine cervical cancer and the expression of HIF-1α due to tissue hypoxia and its impact on radiation response. METHODS: This study is an analytic and observational study with a cross-sectional design with the inclusion criteria in this study that was new cervical cancer Stage IIB, IIIA, IIIB, and IVA patients treated at the oncology polyclinic who had never undergone radiotherapy and would be treated with radiation. RESULTS: Sixty patients advanced cervical cancer aged 25 to &gt;45 years were involved patients. The majority had HPV genotype 16 infections. There was no significant relationship between treatment response and HPV genotype (HPV 16 genotype [p = 0.844], HPV 18 genotype [p = 0.161], other HPV genotypes [p = 0.108]), radiation response with HIF-1α expression (p = 0.503; OR 1.569 [0.417–5.899]), HIF1α expression with HPV genotype (HPV genotype 16 (p = 0.648; OR 1,357 [0.356–5.041]), HPV 18 genotype (p = 0.344; OR 1,458 [0.089–2.373]), and other HPV genotypes (p = 0.505; OR 1.667 [0.368–7.553]) as well as HIF-1α expression and HPV genotypes to radiation response (p &gt; 0.05). CONCLUSION: Cervical cancer with infection with HPV Genotype 18 tends to express HIF1α strongly and increased partial radiation response. Overall statistically, there was no significant association between infection with certain genotypes of HPV with radiation response or HIF-1α expression in tumor tissue with radiation response.

Trends in Metastases among Patients with Masaoka-Koga Stage IV Thymic Epithelial Tumors

Background: Thymic epithelial tumors (TET’s), including thymomas (5 histological subtypes) and thymic carcinomas, are rare tumors with an estimated incidence of 0.15 per 100,000 person-years in the United States. While their etiologies remain largely unknown, some are associated with uniquely high rates of paraneoplastic syndromes and an elevated risk of secondary malignancies. And, though thymomas were once thought to be benign tumors, it is now well-documented that all TET's can metastasize. The gold-standard in TET staging, the Masaoka-Koga system, defines metastatic disease as Stage IV, further specifying pleural/pericardial metastases as Stage IVa and lymphogenous/hematogenous metastases as IVb. Unfortunately, little is known about patient prognosis as it relates to metastasis location. Here, we assemble and analyze one of the largest single-institution databases of TET patients in the world and seek to examine trends in metastases and their correlation with patient prognosis.&#x0D; Methods: Files of 1023 TET patients seen at Indiana University Hospital were accessed via Cerner, after which a standardized information list including demographics, diagnostics, tumor histology, treatments used, disease course, and patient outcome at last follow-up was extracted and input into a RedCap database.&#x0D; Results: Stage IV disease cases were filtered, yielding a total of 428 patients. Of these patients, 122 (29%) had carcinoma, making carcinoma the single largest histology represented in Stage IV. Locations of metastases also varied, with 284 patients (66%) having pleural metastases, 171 (40%) having lung, 71 (17%) liver, 58 (14%) bone, 56 (13%) pericardium, 37 (9%) neck lymph nodes, 12 (3%) brain, and 5 (1%) kidney. Moreover, 98 (23%) patients presented in stage IVb without any pleural/pericardial metastases. At last follow-up, 10% (19) of Stage IVa patients had no recurrence compared to only 3% (7) of IVb patients.&#x0D; Potential Impact: These data altogether suggest that disease spread outside the thorax occurs much more commonly than previously reported, and that rates of metastasis vary with tumor histology. Future analysis will elucidate the exact differences in the patterns of spread among histological types, how these patterns correlate with prognosis, and the implications of this on screening and treatment options.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Oral melanoma: a multicenter study of 69 patients from Japan.

The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). Early detection and radical treatment are essential for improving the prognosis of oral MM patients. Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.

Toripalimab combined with chemoradiotherapy for patients with locally advanced cervical squamous cell carcinoma.

5538 Background: To assess the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma (Chinese Clinical Trial Registry number, ChiCTR2000032879). Methods: Twenty-two locally advanced cervical cancer patients, regardless of programmed death ligand-1 status, received toripalimab treatment combined with concurrent chemoradiotherapy. Concurrent chemoradiotherapy(CCRT) includes cisplatin (40 mg/m2, once a week for 5 weeks), radiotherapy (external irradiation 45-50.4Gy/25-28Fx, 5 fractions a week, followed by brachytherapy 24-30Gy/3-5Fx) and toripalimab (240mg on days 1, 22 and 43). The primary end-point was safety and feasibility. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), overall survival (OS). Results: The median age was 55 years old (range, 42 to 72 years old), with 2 patients in FIGO stage II, 15 patients in stage IIIC, and 5 patients in stage IVA. All patients have received CCRT successfully. Grade III and higher adverse events (AEs) were observed in 10 patients (10/22, 45.5%), and no patient had a grade V AE. The most frequent grade III AE was leukopenia (8/22, 36.4%). The most common immunotherapy-related adverse reaction was hypothyroidism (2/22, 9.1%). The 3-month ORR rate was 95.5%. At data cutoff (Jan 31, 2022), the median follow-up was 10 months (range, 3.30 to 16.73 months). One patient developed multiple metastases 3 months after treatment, and 1 patient developed lung metastasis 6 months after treatment. The ORR was 100%, while the PFS rate was 90.1%, and the OS rate was 95.5%. Conclusions: Toripalimab combined with concurrent chemoradiotherapy demonstrated a manageable safety profile and promising anti-tumor activity in patients with locally advanced cervical cancer, thus might represent a novel treatment option for this patient population. Longer follow-up results and further phase II/III studies are expected. Clinical trial information: ChiCTR2000032879.

Loco-Regional Therapies in Oligometastatic Adrenocortical Carcinoma.

Simple SummaryThe treatment recommended for stage IVa Adrenocortical carcinoma (ACC) not amenable to radical resection is the mitotane plus loco-regional treatment (LR) strategy, which has not yet been validated. Moreover, prognosis factors for this strategy are not yet established. This study aimed to determine which stage IVa ACC patient population would benefit the most from this association. For this purpose, we reviewed all stage IVa patients (≤2 tumoral organs) treated with mitotane and LR from 2008 to 2021 in our institution. This study included 60 patients and 109 LR were performed. The primary endpoint was disease control (DC). We found that DC was associated with longer Time to second line Treatments (TTC). Moreover, DC rate was higher in patients that had ≤5 metastases or a maximum metastasis diameter below 3 cm. Based on those results we propose the first definition of oligometastatic ACC: stage IVa patients with ≤5 metastases or a maximum metastasis diameter below 3 cm. It is vitally important that scientists are able to describe their work simply and concisely to the public, especially in an open-access on-line journal.Objective: The recommended first-line treatment for low-tumor-burden ACC (stage IVa ACC) not amenable to radical resection is mitotane in association with loco-regional treatments (LRs). The aim of this study was to determine the patient population that would benefit the most from LR. Materials and methods: This retrospective monocentric expert center chart review study was performed from 2008 to 2021 and included stage IVa patients (≤2 tumoral organs) treated with LR (either radiotherapy, surgery, or interventional radiology). The primary endpoint was disease control (DC). Correlations between DC, time to systemic chemotherapy (TTC), overall survival (OS), and tumor characteristics were analyzed using Kaplan–Meier survival analysis and Cox’s proportional hazards regression model for multivariate analysis. Results: Thirty-four women (57%) and 26 men with a median age of 48.1 years (IQR: 38.3–59.8) were included. One hundred and nine LRs were performed, with a median of 2 (IQR: 1–3) per patient. DC was achieved in 40 out of 60 patients (66.7%). Patients with DC had a significantly longer TTC (HR: 0.27, p < 0.001) and OS (HR: 0.22, p < 0.001). Patients with less than or equal to 5 metastases (HR: 6.15 (95% CI: 1.88–20.0), p = 0.002) or a maximum metastasis diameter below 3 cm had higher rates of DC (HR: 3.78 (95% CI: 1.09–13.14), p = 0.035). Conclusion: stage IVa ACC patients with ≤5 metastases or a maximum metastasis diameter below 3 cm had favorable responses to LR. We propose the name oligometastatic ACC for this subgroup of patients.

Radio(chemo)therapy in anaplastic thyroid cancer—high locoregional but low distant control rates—a monocentric analysis of a tertiary referral center

BackgroundAnaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival.Patients and methodsA total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates.ResultsMedian follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure.ConclusionDepending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.

Metabolic active tumour volume quantified on [18F]FDG PET/CT further stratifies TNM stage IV non-small cell lung cancer patients.

This study aimed to assess whether the whole body metabolic active tumour volume (MTVWB), quantified on staging [18F]FDG PET/CT, could further stratify stage IV non-small cell lung cancer (NSCLC) patients. A group of 160 stage IV NSCLC patients, submitted to staging [18F]FDG PET/CT between July 2010 and May 2020, were retrospectively evaluated. MTVWB was quantified. Univariate and multivariate Cox regressions were carried out to assess correlation with overall survival (OS). C-statistic was used to test predictive power. Kaplan-Meier survival curves with Log-Rank tests were performed to compute statistical differences between strata from dichotomized variables and to calculate the estimated mean survival times (EMST). Survival rates at 1 and 5 years were calculated. MTVWB was a statistically significant predictor of OS on univariate (p < 0.0001) and multivariate analyses (p < 0.0001). The multivariate model with MTVWB (Cindex ± SE = 0.657 ± 0.024) worked significantly better as an OS predictor than the cTNM model (Cindex ± SE = 0.544 ± 0.028) (p = 0.003). An EMST of 29.207 ± 3.627(95% CI 22.099-36.316) months and an EMST of 10.904 ± 1.171(95% CI 8.609-13.199) months (Log-Rank p < 0.0001) were determined for patients with MTVWB < 104.3 and MTVWB ≥ 104.3, respectively. In subsamples of stage IVA (cut-off point = 114.5) and IVB patients (cut-off point = 191.1), statistically significant differences between EMST were also reported, with p-values of 0.0001 and 0.0002, respectively. In both substages and in the entire cohort, patients with MTVWB ≥ cut-off points had lower EMST and survival rates. Baseline MTVWB, measured on staging [18F]FDG PET/CT, further stratifies stage IV NSCLC patients. This parameter is an independent predictor of OS and provides valuable prognostic information over the 8th edition of cTNM staging.

Prognosis factors of Mitotane and loco-regional treatments combination in low-volume metastatic adrenocortical carcinoma

Recommended first line treatment for low burden IV ACC not amenable for radical resection is mitotane in association with multiple local treatments (M + LT). The aim of this study was to evaluate the efficacy, safety and prognostic factors of M + LT to determine patient population that might benefit the most of this strategy. This retrospective monocentric study performed from 2008 to 2020 included stage IVA patients with ≤ 2 tumoral organs who were treated with M + LT. Primary endpoint was time to chemotherapy (TTC) from mitotane initiation and secondary endpoint were overall survival (OS) and controlled disease (CD) rate. Prognosis factors were analyzed using Kaplan-Meier survival analysis and Cox's proportional hazards regression model. Thirty-four women and 26 men (60/79, 75.9%) with a median age of 48.1 years old (IQR: 38.3-59.8) were included. One hundred and nine LT were performed with a median of 2 (IQR: 1- 3). CDR was 66.6% (40/60). Median TTC was 42 [95%IC: 15 - 100] months. Oligometastatic and CD patients had significantly longer TTC (HR: 0.35, [95%IC 0.18 - 0.68]; HR: 0.27, [95%IC 0.13 - 0.54]). Oligometastatic and patients with only one metastatic organ had significantly longer OS (HR: 0.37, [95%IC 0.18 - 0.77]; HR: 0.30, [95%IC 0.14 - 0.65]). This study supports multiple and combined M + LT to achieve CD. It appears to be particularly efficient in pauci-metastatic ACC as defined by patients with less or equal to 5 metastasis and less than two metastatic organs.

Short and Long-term Outcomes Among High-Volume vs Low-Volume Esophagectomy Surgeons at a High-Volume Center

To determine associations between surgeon volume and esophagectomy outcomes at a high-volume institution. All esophagectomies for esophageal cancer at our institution from August 2005 to August 2019 were reviewed. Cases were divided by surgeon into low, <7 cases/year, vs high volume, ≥7 cases/year, based on Leapfrog Group recommendations. Surgeons remained 'high-volume' after one year of ≥7 cases. Demographics, comorbidities, course of care, and long-term outcomes were compared. In total, 1029 cases were evaluated; 120 performed by low-volume surgeons vs 909 by high-volume surgeons. Never-smokers, atrial fibrillation, and clinical Stage IVa patients were associated with high-volume surgeons. Other demographics were similar. Low-volume surgeons did more open cases, 45.8% vs 14.5%, P < 0.01. Low-volume surgeons had more complications than high-volume surgeons (71.7% vs 57.6%, P < 0.01), specifically Grade II and III (59.2% vs 46.8%, P=0.01, and 44.2% vs 27.0%, P <0.01). No differences were seen in anastomotic leak rate, 90-day mortality, recurrences, 5-year overall survival (46.7% low-volume vs 49.3% high-volume, P=0.64), or 5-year disease-free survival (35.7% low-volume vs 42.2% high-volume, P=0.27). In multivariable logistic regression for Grade III or higher complications, high-volume surgeons had an odds ratio of 0.56 (95% confidence interval 0.36-0.87) for complications. Our study found higher rates of open esophagectomies and complications in low-volume esophagectomy surgeons compared to high-volume surgeons at the same, high-volume institution. However, low-volume surgeons were not associated with worse survival outcomes compared to high-volume surgeons. Low-volume esophagectomy surgeons may benefit from mentoring and support to improve perioperative outcomes; these efforts are underway at our institution.