Chemotherapy Regimens Research Articles

EP362 - Small Cell Ca of the Gall Bladder: A rare tumour of the gall bladder

Abstract Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumour. Despite aggressive and varied treatments, its prognosis is poor. A 53/F presented with complaints of pain in abdomen and fever since 3 days. Patient was vitally stable and tenderness present over the epigastric, Right hypochondrium and Right lumbar region. Except leucocytosis, all labs were WNL. CECT Abdomen pelvis was suggestive of suspicious Gall bladder perforation with necrotic lymph nodes in the peri-pancreatic region. The patient was taken for exploratory laparotomy and a perforated gall bladder was seen intra op and cholecystectomy was performed. Histopathology findings were suggestive of small cell carcinoma - gall bladder and IHC markers (Synaptophysin, CD56, Ki67, EMA, CK19) sent for confirmatory findings were raised. Post op PET CT shows periportal, paracaval and aortocaval metastatic lymph nodes. Chemotherapy regimen (cisplatin + itoposide) was started post op and patient is under follow up. The incidence of SCC of the GB is approximately 0.5% of all GB cancers. Among NETs of the gastrointestinal tract, SCC of the GB compromises 0.2%. Less than 100 cases of this tumour have been documented in the English literature. Surgery is the mainstay of GB cancer treatment. Due to poor prognosis of SCC of the GB, even when curative surgery is possible, additional treatment methods such as chemoradiation should be considered.

Induction prior to autologous haematopoietic cell transplantation in multiple myeloma.

Induction chemotherapy followed by autologous haematopoietic cell transplantation and post-transplant therapy (including maintenance therapy with or without prior consolidation) is still considered as the standard of care for newly diagnosed young and fit multiple myeloma patients. Over the last years, superiority of quadruplet regimens for induction was established, with the addition of an anti-CD38 monoclonal antibody to triplet regimen including a proteasome inhibitor, an IMiD (thalidomide or lenalidomide) or cyclophosphamide, and dexamethasone. Given quadruplet induction regimens are associated with deep response, including a high-rate of sustained measurable residual disease negativity in a significant proportion of patients, they are now recommended for induction chemotherapy when available.

Extra-abdominal and intra-abdominal FET::CREM fusion mesenchymal neoplasms: comparative clinicopathological study of 9 new cases further supporting a distinct potentially aggressive sarcoma and report of novel sites.

With the wide use of RNA sequencing technologies, the family of FET::CREB fusion mesenchymal neoplasms has expanded rapidly to include potentially aggressive neoplasms, not fitting any well established WHO entity. Recently, a group of intra-abdominal FET(EWSR1/FUS)::CREB(CREM/ATF1) fused unclassified neoplasms has been reported followed by recent recognition of an analogous extra-abdominal category of unclassified neoplasms carrying EWSR1::ATF1 fusions. We describe 9 additional tumors (5 extra-abdominal and 4 abdominal) carrying an EWSR1::CREM (n = 8) and FUS::CREM (n = 1) fusion. Patients were 7 females and 2 males aged 10 to 75years (median, 34). Extra-abdominal tumors originated in the head and neck (2 sinonasal, 1 orbital) and soft tissues (1 gluteal, 1 inguinal). Abdominal tumors involved stomach (2), mesentery (1), and kidney (1). Tumor size ranged from 3.5 to 11cm (median, 6). Treatment was radical surgery with (5) or without (2) neo/adjuvant radio/chemotherapy. Extended follow-up of 5 patients (21-52months; median, 24) showed an aggressive course in two (40%); one died of disseminated metastases 52months after several intensified chemotherapy regimens, and one was alive with progressive abdominal disease at 21months. The immunophenotype of the two subcohorts was significantly overlapping with variable expression of EMA (7 of 8), keratin AE1/AE3 (5 of 9), CD99 (4 of 7), MUC4 (2 of 8), ALK (3 of 8), synaptophysin (3 of 9), chromogranin (1 of 8), CD34 (3 of 6), CD30 (1 of 6), PAX8 (1 of 7), and inhibin (1 of 7), but no reactivity with desmin (0 of 8), S100 (0 of 8), and SOX10 (0 of 8). This series further solidifies the notion that FET::CREB fusions are not limited to the triad of angiomatoid fibrous histiocytoma, clear cell sarcoma, and malignant gastrointestinal neuroectodermal tumor, but characterize an emerging family of potentially aggressive neoplasms occurring at both intra- and extra-abdominal sites. These tumors underscore the promiscuity of the FET::CREB fusions and highlight the pivotal role of phenotype-oriented classification of these neoplasms that share the same genotype, still featuring significant biological and behavioral distinctness.

The Impact of Sugar Control on Pancreatic Cancer Progression for the Elderly

Pancreatic cancer is a type of cancer that originates in the pancreas, an organ that aids in digestion and blood sugar regulation. It is characterized as an aggressive type of cancer that presents with symptoms that often go undetected. In 2024, there were an estimated 66,440 new cases of pancreatic cancer and an estimated 51,170 deaths from pancreatic cancer, with a 5-year relative survival rate of 12.8% (SEER, 2023). While traditional medical interventions such as surgery and chemotherapy continue to be the cornerstone of treatment, there is an emerging focus on the potential impact of dietary and nutritional factors in both preventing and managing pancreatic cancer. This approach is particularly relevant for elderly patients due to the heightened risk associated with surgery at their age and their reduced tolerance to chemotherapy regimens. This paper presents a compelling case study of a pancreatic cancer patient who adopted a sugar-restricted diet, resulting in a notable decrease in the tumor marker CA 19-9, which is commonly associated with pancreatic cancer. Building on this individual case study, this paper provides a comprehensive review of current scientific literature to examine the potential relationship between sugar consumption and pancreatic cancer development and progression. By examining this intersection of nutrition and oncology, this study aims to expound upon possible alternative or complementary approaches to pancreatic cancer management, especially for vulnerable populations such as the elderly. This research could lead to new strategies for improving outcomes and quality of life in pancreatic cancer care.

Bortezomib, lenalidomide, and dexamethasone versus bortezomib, doxorubicin, and dexamethasone in newly diagnosed multiple myeloma

Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution.

T lymphocyte‑related immune response and immunotherapy in gastric cancer (Review).

Gastric cancer (GC) remains a global healthcare challenge because of its high incidence and poor prognosis. The efficacy of current chemotherapy regimens for advanced GC is limited. T cells, which have been implicated in the progression of GC, have a significant impact in the tumor microenvironment. With a more detailed understanding of the mechanisms underlying the cancer immunoediting process, immunotherapy may become a promising treatment option for patients with GC. Several clinical trials are currently investigating different mechanisms targeting the tumor immune response. The present review summarized T cell-involved immune responses and various immunotherapy strategies for GC.

Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of ‘two points of intraneural (endoneural) invasion in the case of four pathological slides’ has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.

Treatment strategies for elderly patients with locally advanced esophageal cancer: a systematic review and meta-analysis

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by surgery remains a standard of care for resectable esophageal cancer (EC), and definitive chemoradiotherapy (dCRT) is an alternative for unresectable diseases. However, it is controversial for the use of the two aggressive regimens in elderly patients.MethodsWe systematically searched multiple databases for studies comparing overall survival (OS) and/or progression-free survival (PFS) between dCRT and surgery (nCRT + surgery or surgery alone) or between dCRT and radiotherapy (RT) alone in elderly patients (age ≥ 65 years) until March 28, 2024. Statistical analysis was performed using random-effects model.ResultsFourty-five studies with 33,729 patients were included. dCRT significantly prolonged OS (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.58–0.70) and PFS (HR = 0.67, 95% CI: 0.60–0.76) compared to RT alone for unresectable EC, and resulted in a worse OS compared to surgery for resectable cases (HR = 1.34, 95% CI: 1.23–1.45). Similar results of OS were also observed when the multivariate-adjusted HRs were used as the measure of effect (dCRT vs. RT alone: HR = 0.65, 95% CI: 0.58–0.73; dCRT vs. surgery: HR = 1.49, 95% CI: 1.28–1.74). Subgroup analyses according to age group (≥ 70, ≥ 75, or ≥ 80 years), study design, study region, histological type, radiation field, chemotherapy regimen revealed comparable results.ConclusionsnCRT + surgery is likely a preferred strategy for elderly patients with good physiological conditions; and dCRT is a better alternative for unresectable cases. Advanced age alone does not appear to be a key predictor for the tolerability of the two aggressive treatments.

Melatonin mitigates chemotherapy-induced small intestinal atrophy in rats and reduces cytotoxicity in murine intestinal organoids.

Cancer continues to pose a significant global health challenge, with gastrointestinal (GI) cancers among the most prevalent and deadly forms. These cancers often lead to high mortality rates and demand the use of potent cytotoxic chemotherapeutics. For example, 5-fluorouracil (5-FU) forms the backbone of chemotherapy regimens for various GI cancers, including colorectal cancer. While these chemotherapeutics efficiently kill cancer cells, they frequently cause off-target effects such as chemotherapy-induced mucositis (CIM), characterized by debilitating symptoms like pain, nausea, and diarrhoea, necessitating medical intervention. In this study, we elucidated the potential of melatonin and misoprostol to reduce 5-FU-induced small intestinal mucositis. Morphological and cellular changes in the jejunum, along with colonic faecal water content were quantified in rats as markers for CIM. Additionally, the effects of melatonin were investigated in vitro on 5-FU treated murine intestinal organoids. The results showed that melatonin prevented villus atrophy in the rat jejunal mucosa and upheld cell viability in murine intestinal organoids. In contrast, misoprostol alone or in combination with melatonin did not significantly affect CIM caused by 5-FU. These in vivo and in vitro experiments provided promising insights that melatonin may be used as a preventive and/or adjuvant combination therapy to prevent and reduce CIM, holding the potential to enhance cancer treatment outcomes and improve patient quality-of-life.

PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology.

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity.

Impact of an Etoposide Chemotherapy Shortage on Patients With Extensive-Stage Small-Cell Lung Cancer: Results of a Natural Experiment.

A shortage of essential intravenous (IV) etoposide lasted from 2018 until 2020 in Ontario, Canada, allowing for a natural experiment in which external factors (IV etoposide availability) dictated patients' treatment assignment. The purpose of this study was to evaluate the impact of this IV etoposide shortage (IVES) on patient care outcomes. Individuals with extensive-stage small-cell lung cancer (ES-SCLC) treated during a pre-IVES (November 2017-October 2018) and IVES (November 2018-October 2019) time intervals were retrospectively reviewed at the Verspeeten Family Cancer Centre. We investigated the association of the shortage on health care utilization and survival using a time-to-event analysis, Cox proportional hazards and logistic regression modeling. A total of 119 patients with ES-SCLC were assessed, 49 in the pre-IVES interval and 70 in the IVES interval. The median age was 68 (IQR, 62-74) years, 48% (n = 57) were male, 33% (n = 39) had CNS metastases, and 69% (n = 82) received first-line systemic therapy. Alternate regimens used for IVES cohort included IV platinum-oral (PO) etoposide, IV platinum-IV irinotecan, and PO etoposide monotherapy. An adjusted multivariable model demonstrated a significant increase in hospitalization (odds ratio, 2.30 [95% CI, 1.01 to 5.24]; P = .047) and shorter progression-free survival (PFS; hazard ratio, 1.79 [95% CI, 1.19 to 2.68]; P = .005) during the IVES. This study demonstrated increased hospitalization, and decreased PFS, among patients with ES-SCLC treated with alternate chemotherapy regimens during an IVES. The impact of cancer drug shortages can be harmful, and optimizing a more secure drug supply with mitigation strategies is warranted.

Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumor.

Cancer stem cells (CSCs) in colorectal cancer (CRC) drive intratumoral heterogeneity and distant metastases. Previous research from our group showed that CSCs can be easily detected by autofluorescence (AF). The aim of the present study was to evaluate the potential role of AF CSCs as a prognostic biomarker for CRC relapse. Seventy-five freshly-resected tumors were analyzed, by flow cytometry. AF was categorized as high (H-AF) or low (L-AF), and results were correlated with histological features (grade of differentiation, presence of metastases in lymph nodes (LN), perivascular and lymphovascular invasion) and clinical variables (time to relapse and overall survival). Nineteen out of 75 (25.3%) patients experienced relapse (local or distant), 13 out of these 19 patients showed positive LNs and 6 patients had H-AF. Of note, 4 of them died before 5 years. While patients with H-AF CSCs percentages in the global population experienced 1.5 times increased relapse -HR 1.47, CI 95% (0.60 - 3.63), patients with H-AF CSC percentages and LN metastases had the highest risk of relapse; HR 7.92, p< 0.004, CI 95% (1.97 - 31.82). These data support AF as an accurate and feasible marker to identify CSCs in resected CRC. A strong statistical association between H-AF CSCs and the risk of relapse was observed, particularly in patients with positive LNs, suggesting that H-AF patients might benefit from adjuvant chemotherapy regimens and intensive surveillance due to their high propensity to experience disease recurrence.

Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets.

The accumulation of senescent cells is thought to play a crucial role in aging-associated physiological decline and the pathogenesis of various age-related pathologies. Targeting senescence-associated cell surface molecules through immunotherapy emerges as a promising avenue for the selective removal of these cells. Despite its potential, a thorough characterization of senescence-specific surface proteins remains to be achieved. Our study addresses this gap by conducting an extensive analysis of the cell surface proteome, or "surfaceome", in senescent cells, spanning various senescence induction regimes and encompassing both murine and human cell types. Utilizing quantitative mass spectrometry, we investigated enriched cell surface proteins across eight distinct models of senescence. Our results uncover significant changes in surfaceome expression profiles during senescence, highlighting extensive modifications in cell mechanics and extracellular matrix remodeling. Our research also reveals substantive heterogeneity of senescence, predominantly influenced by cell type and senescence inducer. A key discovery of our study is the identification of four unique cell surface proteins with extracellular epitopes. These proteins are expressed in senescent cells, absent or present at low levels in their proliferating counterparts, and notably upregulated in tissues from aged mice and an Alzheimer's disease mouse model. These proteins stand out as promising candidates for senotherapeutic targeting, offering potential pathways for the detection and strategic targeting of senescent cell populations in aging and age-related diseases.

Vaginal dinoprostone insert compared with two different oral misoprostol regimens for labor induction in nulliparous and multiparous women.

Labor induction exhibits considerable variations in protocols and medication regimens. Limited studies compare vaginal dinoprostone inserts with different oral misoprostol dosages, considering parity influence. This study explores the distinctions among 10 mg vaginal dinoprostone inserts and oral misoprostol 25 μg every 2 and every 4 h for labor induction, stratified by parity. This retrospective cohort study involved 607 participants across two hospitals. The primary outcome, time from induction to delivery, and secondary outcomes, including mode of delivery and maternal and fetal safety, were assessed. Patient characteristics revealed differences in indication for labor induction, with the dinoprostone cohort having fewer post-term and premature rupture of membranes cases but more intrauterine growth restriction/small-for-gestational age. Both oral misoprostol regimens showed a shorter time to delivery interval compared to the dinoprostone cohort (median: 1380 min [IQR 1381.0] and 1127.0 min [IQR 1214.0] versus 1631.5 [IQR 1736.2], p < 0.001 and p = 0.014). Only the difference between oral misoprostol q2h and vaginal dinoprostone remained significant for nulliparous but not multiparous women, losing significance over all the population after adjusting for confounding factors. The proportion of women giving birth within 24 h did not significantly differ between misoprostol q2h and dinoprostone after adjusting for confounders. When comparing misoprostol q4h with dinoprostone after confounder adjustment, an increased time to delivery interval for misoprostol q4h was found (p = 0.001). Both oral misoprostol regimens exhibited fewer meconium-stained liquor (miso q4h: OR 0.44, miso q2h: OR 0.34) and cesarean sections (miso q4h: OR 0.48, miso q2h: OR 0.53) compared to dinoprostone, even after adjustment for confounders. Our study suggests that oral misoprostol 25 μg q4h is less effective than 10 mg vaginal dinoprostone for labor induction if parity and indication for induction are adjusted for, particularly in multiparous women. In terms of side effects, oral misoprostol regimens seem superior to vaginal dinoprostone. Our data support the individualized use of different agents for labor induction according to parity, indication for induction, bishop score, and women's preference.

Exploring Genetic Variants and Platinum Chemotherapy Response in Indonesian Non-Small Cell Lung Cancer Patients: Insights from ERCC2 rs13181.

Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While ERCC2 is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic. This study recruited 82 NSCLC patients with wildtype mutations of EGFR at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy. The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between ERCC2 rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292-3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263-3.568; p=0.963). This study did not find statistically significant associations between ERCC2 rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations.

54078 Examining Hair Preservation in Manual vs. Machine Scalp Cooling by Chemotherapy Regimen: A Meta-Analysis

54078 Examining Hair Preservation in Manual vs. Machine Scalp Cooling by Chemotherapy Regimen: A Meta-Analysis

245. ESOPHAGECTOMY AFTER NEOADJUVANT CHEMOTHERAPY WITH AN INDICATION FOR CONVERSION SURGERY FOR HIGHLY ADVANCED ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA

Abstract Background There is currently no strong evidence for preoperative chemotherapy for advanced esophagogastric junction adenocarcinoma. Furthermore, no curative treatment strategy has been established for advanced junction adenocarcinoma, including Stage IV disease, with no indication for conversion surgery. Subjects and Methods In this study, we retrospectively reviewed nine patients with highly advanced esophagogastric junctional adenocarcinoma, including Stage IV adenocarcinoma, who underwent systemic chemotherapy followed by planned resection at our hospital. Results The participants included 6 males and 3 females, with median age of 64 (range: 45–72) years. Pretreatment stages III, IVA, and IVB, categorized based on UICC TNM classification (esophageal adenocarcinoma), were observed in 1, 4, and 4 cases, respectively, with 1 case of (#104) subclavian lymph node metastases, 1 case of (#16) abdominal para-aortic lymph node metastases, and 2 cases of liver metastases, including multiple lesions. All patients received S-1 plus oxaliplatin (SOX) therapy as preoperative chemotherapy (2–40 courses). Although we observed one patient with unresectable abdomen malingnancies, the others underwent R0 resection, six underwent esophagectomy (with three total gastrectomy and one liver resection), and two open (+ continuous right thoracotomy) lower esophagectomy + total gastrectomy. Pathological stages I, II, III, and IV were observed in two, one, four, and one patients, respectively. Postoperatively, stereotactic irradiation, chemotherapy, and immune checkpoint inhibitors were administered to the patients to treat recurrent brain and liver metastases, and the 1-year survival rate was found to be 71.4% with a median observation period of 17 (range: 0–61) months. Among them, downstage and pN0 cases were relatively promising. Conclusion Even in highly advanced cases, cases with promising prognoses with multidisciplinary treatment, including surgery, were observed. We hope that large-scale clinical trials, such as JCOG2203, will help clarifying the significance of this approach, and advancements in chemotherapy regimens are expected.

Weekly versus 2-weekly versus 3-weekly docetaxel to treat metastatic castration-resistant prostate cancer

BackgroundTo compare the efficacy and toxicity of docetaxel treatment regimens in metastatic castration-resistant prostate cancer (mCRPC). MethodsWe retrospectively analyzed 162 patients diagnosed with mCRPC who underwent docetaxel chemotherapy between 2009 and 2020. The subjects were divided into three groups according to the dosage and interval of docetaxel (DCT) chemotherapy regimen: 30 mL/m2 weekly, 50 mL/m2 2-weekly (every 2 weeks), and 75 mL/m2 3-weekly (every 3 weeks). ResultsThere were no significant differences in the prostate specific antigen (PSA) response rates (p = 0.709). The median time to progression was 3.0 (IQR 2.0-5.3) months, 5.0 (IQR 2.0-13.0) months, and 5.0 (IQR 3.0-12.0) months in the weekly, biweekly, and triweekly groups, respectively (p = 0.062). The median overall survival (OS) was 12.5 (IQR 6.0-14.0) months, 18.8 (IQR 5.5-23.5) months, and 22.9 (IQR 11.0-33.0) months in the weekly, biweekly, and triweekly groups, respectively (p < 0.001). There were no differences in all toxicity and grade 3 or higher toxicity. In Cox multivariate regression analysis, the Eastern Cooperative Oncology Group performance status (ECOG-PS), response to chemotherapy, and chemotherapy cycle also affected the PFS. Age, ECOG-PS and chemotherapy cycle affected the OS. ConclusionsThe various options for optimal chemotherapy are indicated depending on the patient's conditions during the diagnosis of mCRPC. Treatment with DCT at 2-week or even 1-week intervals appears to be well tolerated in men diagnosed with mCRPC and represents a useful option when the conventional triweekly regimen is not tolerated due to poor patient condition.

624. LONG-TERM OUTCOME OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY ESOPHAGECTOMY VERSUS DEFINITIVE PROTON BEAM THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Proton beam therapy (PBT) for esophageal squamous cell carcinoma (ESCC) is a promising curable treatment to avoid surgery, however the long-term outcomes have not enough been reported. Herein, we compared the survival outcomes of PBT with those of esophagectomy after neoadjuvant chemotherapy, which is the standard of care in Japan. Methods Patients with thoracic ESCC, clinical stage II or III, who underwent neoadjuvant chemotherapy plus radical resection and proton beam therapy between 2011 and 2020 were identified from database of our institute. The chemotherapy regimen was 5FU, CDDP (CF) with/without docetaxel. PBT was defined as irradiation of 50 GyE or more to the primary tumor, prophylactic irradiation, and concurrent chemotherapy (CF). Patients with other severe diseases and patients who could not be followed up were excluded. To adjust confounding factors, propensity score matching was performed; covariates included T and N-factor, age, gender, time of treatment and site of tumor. We retrospectively evaluated overall survival time of the surgery and PBT groups as primary outcome in this study. Results 244 patients were selected from the database. Median age was 71 years, 209 were male, 102 had esophagectomy after chemotherapy, and 142 had PBT. After propensity score matching, 46 patients in each group were selected by propensity score matching. Median survival was 42.8:44.6 months in the surgery and PBT groups, respectively (p=0.784). There were no treatment-related deaths, and Grade 3 or higher adverse events occurred in 8 and 8 patients (p=1.00), respectively. Conclusion PBT for stages II and III ESCC was comparable to neoadjuvant chemotherapy followed by surgery in long-term outcomes and adverse events.

The surgical, histopathological characteristics, and survival outcome of ovarian clear cell carcinoma: a retrospective case series sharing the experience of a tertiary cancer centre.

Ovarian clear cell carcinoma (OCCC) is a rare and distinct subtype of epithelial ovarian cancer (EOC). It is unique in several biological aspects. This study analyzes the clinicopathological features and survival outcome of patients with OCCC, aiming to identify factors affecting recurrence, progression-free survival (PFS) and overall survival (OS). A retrospective study included 49 women with OCCC between January 2009 and December 2021 at Oxford Cancer Center. All demographic and pathological characteristics, pre-operative biomarkers, surgical procedure, complications, hospital stay, chemotherapy regimen, and disease status on follow-up, were collected from electronic medical records. No residual disease (R0) was achieved in 39 out of 49 women who underwent cytoreductive surgery. The follow-up time had a mean of 8.75 years. The 3-year OS was 73.4%, and the 3-year PFS was 81.3% [95% confidence interval (CI): 84.63-118.93]. Women with stage 1 disease had the best outcome. There was a marked difference (P<0.001) in OS in the presence of residual disease. No residual disease conferred a 3-year OS of 88.6% (95% CI: 108.6-141.8), compared to only 12.5% in the presence of residual disease (95% CI: 4.48-32.11). In multivariant analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage was the only independent prognostic indicator of OS with (P<0.05), including carbohydrate antigen (CA) 125, hemoglobin, albumin, associated endometriosis, ascites, residual disease and FIGO staging. Surgery to achieve no residual disease is necessary to improve the prognosis in advanced OCCC. The true challenge is to predict which patients with early-stage disease at higher risk of recurrence and would most benefit from adjuvant treatments.