First-line Palliative Chemotherapy Research Articles

A rapid assessment tool for systemic treatment outcomes in colorectal cancer with deep bidirectional transformers.

e15567 Background: Retrospective investigations involving cancer treatment encounter the challenge of manually reviewing voluminous imaging reports to identify the best responses and the timing of disease progression. Here, we employed natural language processing, specifically deep bidirectional transformers, to automate the extraction of treatment response data. Methods: Data were sourced from the Yonsei Cancer Data Library database, focusing on patients with stage II-IV colorectal cancer at the Yonsei Cancer Center from Jan 1, 2010, to Dec 31, 2020. Imaging reports from 6,574 patients were gathered, amounting to 97,119 CT readings. Among these, 9,000 CT reports corresponding to 2,859 patients were randomly subjected to multilabel manual labeling by four radiology experts, based on the RECIST version 1.1 classification (CR/NED, PR, SD, PD). The pretrained BERT-base-uncased model was employed and fine-tuned for the downstream tasks of multilabel classification. 6,765 reports were used for training, while the remaining 1,000 reports were divided equally between the validation and test sets. Additionally, an algorithm for integrating and extracting treatment response data was also implemented. Clinical data were meticulously collected for 47 patients with stage IV early-onset colorectal cancer (EOCRC) receiving palliative first-line chemotherapy. The primary objective was to evaluate the model’s accuracy in predicting the timing of disease progression events within a ±30-day window. Secondary objectives focused on the model’s ability to identify the best response and its timing within a ±45-day window. Results: The evaluation of the classification accuracy across 1,000 individual CT reports, categorized as CR/NED (319), PR (86), SD (272), and PD (298), revealed accuracy with an AUROC of 0.956 and an F1 score of 0.823. All EOCRC patients were initially diagnosed with stage IV disease, and 45 out of 47 (95.7%) underwent metastasectomy either before initiating chemotherapy or during the first-line chemotherapy treatment. In clinical evaluation, the model demonstrated 72.3% (95% Confidence Interval [CI], 59.5-85.1) accuracy in predicting the day of disease progression within a ±30-day window. It achieved 55.3% (95% CI, 41.1-69.5) accuracy in predicting the best response category and its timing within ±45-days. Notably, the model was more accurate in predicting CR/NED at 72% compared to SD and PR, which had accuracy of 27.3% and 15.4%, respectively. Conclusions: Our model demonstrated high performance in classifying CT reports, which is expected to provide rapid insights into patient progress and improve clinical decision-making. However, the complexity involved in integrating and extracting data result in slight constraints in performance. This emphasizes the need for further research into multimodal large language models that can integrate a wider variety of clinical data.

Abstract PO1-05-14: Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer

Abstract Background: Visceral crisis (VC) in metastatic breast cancer (BC) is defined as severe organ dysfunction, as assessed by signs and symptoms, laboratory tests, and rapid disease progression. The management of this condition is currently based on limited retrospective evidence and expert opinions, since VC has been a common exclusion criterion in clinical trials. There is a paucity of real-world data regarding the management of BC VC. We aim to evaluate the survival outcomes and prognostic factors of first-line palliative chemotherapy for VC in a tertiary cancer center in Brazil. Methods: Data were retrospectively collected from patients with metastatic BC diagnosed with VC between 2017 and 2022 in a single cancer center. Our analysis focused on patients receiving first-line chemotherapy for VC. Patients with hormone receptor-positive BC could have been previously treated with endocrine therapy for metastatic disease. CDK4/6 inhibitors were not available in the cancer center during the study period. Prognostic factors associated with survival were evaluated through univariate and multivariable analyses, using the Cox regression model. Results: A total of 106 patients with VC were evaluated. Among them, 58.5% (62 patients) had not received any previous line of chemotherapy in the metastatic setting before the diagnosis of VC (1st line cohort). Median overall survival (mOS) in the total population was 1.7 months, significantly distinct from the 1st line cohort, which had a mOS of 4.9 months (p < 0.001). Focusing on the 1st line cohort, the most common type of VC was pulmonary (40.3%), followed by hepatic (24.2%), and medullary infiltration (21%). 66.1% of patients had HR+HER2- (mOS 9.3 months), 19.3% HER2+ (mOS 4.5 months), and 11.3% triple-negative BC (TNBC) (mOS 1.5 months). Most patients were treated for VC based on systemic therapy combinations (59.7%), while 32.2% received monochemotherapy, and 8.1% were managed with best supportive care (BSC) alone. In the population receiving multidrug therapy, the mOS was 9.3 months, compared to 4.9 months with monochemotherapy and 0.7 months in patients undergoing BSC. Nevertheless, the type of treatment received was not associated with OS in the multivariable analysis. In the multivariable analysis, the prognostic factors associated with worse mOS were TNBC subtype, hepatic VC), and ECOG-PS > 2. (Table). Among patients with hepatic VC, 73.7% died during the same hospitalization and 60.5% received chemotherapy within 30 days prior to death. Conclusions: Patients with VC due to BC have a poor prognosis, even in the context of first-line chemotherapy. Factors such as ECOG-PS, BC subtype, and VC type should be taken into account when discussing the expected outcomes of this life-threatening condition. Taking these factors into account can help physicians to differentiate patients who are more likely to benefit from systemic oncologic treatment from those for whom such therapy would be futile or potentially harmful. Median overall survival according to baseline characteristics and multivariable analysis (1st line cohort, n=62) Citation Format: Matheus de Oliveira Andrade, Vitor Hugo Felix, Renata Colombo Bonadio, Laura Testa. Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-14.

HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.

Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System

AimsClinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. Materials and methodsUsing linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. ResultsWe identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). ConclusionsIn this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

Abdominal Visceral-to-Subcutaneous Fat Volume Ratio Predicts Survival and Response to First-Line Palliative Chemotherapy in Patients with Advanced Gastric Cancer.

Prognosis in advanced gastric cancer (aGC) is predicted by clinical factors, such as stage, performance status, metastasis location, and the neutrophil-to-lymphocyte ratio. However, the role of body composition and sarcopenia in aGC survival remains debated. This study aimed to evaluate how abdominal visceral and subcutaneous fat volumes, psoas muscle volume, and the visceral-to-subcutaneous (VF/SF) volume ratio impact overall survival (OS) and progression-free survival (PFS) in aGC patients receiving first-line palliative chemotherapy. We retrospectively examined CT scans of 65 aGC patients, quantifying body composition parameters (BCPs) in 2D and 3D. Normalized 3D BCP volumes were determined, and the VF/SF ratio was computed. Survival outcomes were analyzed using the Cox Proportional Hazard model between the upper and lower halves of the distribution. Additionally, response to first-line chemotherapy was compared using the χ2 test. Patients with a higher VF/SF ratio (N = 33) exhibited significantly poorer OS (p = 0.02) and PFS (p < 0.005) and had a less favorable response to first-line chemotherapy (p = 0.033), with a lower Disease Control Rate (p = 0.016). Notably, absolute BCP measures and sarcopenia did not predict survival. In conclusion, radiologically assessed VF/SF volume ratio emerged as a robust and independent predictor of both survival and treatment response in aGC patients.

Histologic subtype-based evaluation of recurrence and survival outcomes in patients with adenocarcinoma of the ampulla of Vater

Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3–49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04–3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11–3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19–9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23–4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.

2069P QoL changes of caregivers during first-line palliative chemotherapy for patients with incurable cancer

2069P QoL changes of caregivers during first-line palliative chemotherapy for patients with incurable cancer

Duodenal Metastasis from Colorectal Cancer: A Case Report

Background: The occurrence of metastatic colon lesions in various organs has been documented extensively in the literature. The liver, lungs, and bones are the most frequently affected sites. Metastasis in the duodenum due to colon cancer is an infrequent occurrence. Case Presentation: We present a detailed case report of a 65-year-old female patient diagnosed with metastatic colon cancer to the duodenum. The patient initially underwent extended right hemicolectomy for stage III low-grade adenocarcinoma of the colon. Adjuvant chemotherapy was administered, resulting in a period of apparent remission. However, in 2020, the patient experienced elevated tumor marker levels, prompting further investigations. Endoscopy revealed an irregular mass infiltrating the muscle layer in the duodenum, confirming malignant involvement. The patient underwent curative distal gastric duodenectomy, with pathology results indicating a colonic origin of the tumor. The patient received first-line palliative chemotherapy with FOLFOX rechallenge and the addition of AVASTIN. Several cycles of chemotherapy were completed, with satisfactory tumor response observed in follow-up PET scans. Maintenance therapy was initiated after achieving disease-free status on CT scans. However, in October 2022, the patient exhibited increasing tumor marker levels and new findings on PET scan, leading to the initiation of second-line palliative therapy with FOLFIRI and ramucirumab. The patient has received multiple cycles of second-line therapy, with the most recent PET scan in February 2023 showing a favorable treatment response, including a decrease in the size of existing nodes and no identification of new lesions. Conclusion: In conclusion, this case exemplifies the journey of a patient with stage 3 colon cancer who initially responded well to surgery and adjuvant chemotherapy, but experienced subsequent relapse in the duodenum. Despite surgical intervention and palliative chemotherapy, the patient developed metastasis in the liver, lung, and multiple lymph nodes.

A Novel Hematological Inflammation-Nutrition Score (HINS) and Its Related Nomogram Model to Predict Survival Outcome in Advanced Gastric Cancer Patients Receiving First-Line Palliative Chemotherapy.

This study aims to construct a novel hematological inflammation-nutrition score (HINS) and investigate its prognostic value in patients with advanced gastric cancer (AGC). We investigated the risk stratification performance of HINS and developed a HINS-based nomogram model to predict overall survival by combining traditional predictors. We conducted a retrospective study on 812 AGC patients who received first-line platinum- or fluoropyrimidine-containing chemotherapy at The First Affiliated Hospital of Zhengzhou University Hospital between 2014 and 2019. Patients were randomly divided into a training cohort (N=609) and a validation cohort (N=203). HINS (0-2) was constructed based on a pre-chemotherapy systemic immune-inflammation index (SII) and albumin (ALB). Prognostic factors were screened by univariate and multivariate COX proportional regression models. Significant factors were used to construct a nomogram model. Internal validation was performed by calibration curves, time-dependent receiver operating characteristics (ROC) curves, and decision curve analysis (DCA), evaluating its prediction consistency, discrimination ability, and clinical net benefit. HINS was constructed based on SII and ALB. HINS showed a better stratification ability than JCOG prognostic index, with significant differences between groups. Multivariate analysis showed that ECOG ≥1 (HR: 1.379; P=0.005), Stage IV (HR: 1.581; P <0.001), diffuse-type histology (HR: 1.586; P <0.001), number of metastases ≥2 (HR: 1.274; P=0.038), without prior gastrectomy (HR: 1.830; P <0.001), ALP ≥ULN (HR: 1.335; P=0.034), HINS (P <0.001) were independent factors of OS. We successfully established a HINS-based nomogram model that showed a strong discriminative ability, accuracy, and clinical utility in training and validation cohorts. HINS shows a superior risk stratification ability, which might be a potential prognostic biomarker for AGC patients receiving palliative first-line palliative chemotherapy. The HINS-based nomogram model is a convenient and efficient tool for managing prognosis and follow-up treatments.

Determinants of Treatment Toxicity in Patients with Soft Tissue Sarcomas

Soft tissue sarcomas are rare malignant tumors. Traditionally, treatment is guided by patient and tumor characteristics. Data on the influence of patient characteristics, particularly nutritional status, on clinical outcomes are scarce. Body composition and its changes during treatment play an essential role in predicting toxicity, clinical outcomes, and mortality. This analysis aimed to investigate the relationship between treatment toxicity and body composition. Patients diagnosed with sarcoma who underwent first-line palliative chemotherapy between October 2017 and January 2020 were included. Baseline and follow-up computed tomographic scans at the third lumbar vertebra, available from diagnostic purposes, were analyzed using SliceOmatic software. Treatment toxicity was defined as a composite score of the Common Terminology Criteria for Adverse Events. Nutritional Risk Screening (NRS) 2002 score, psoas muscle thickness to height ratio, and comorbidity showed a significant association with overall toxicity, while skeletal muscle index and age showed a strong trend. In summary, the NRS 2002 tool must be routinely implemented in inpatient and outpatient settings for cancer patients, and nutritional therapy needs to become a fixed component of multimodal cancer treatment. Furthermore, validated standardized procedures for the quantification of muscle mass are needed to individualize and optimize cancer treatment.

Prognostic value of Lynch syndrome, BRAFV600E , and RAS mutational status in dMMR/MSI-H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts.

Current knowledge on prognostic biomarkers (especially BRAFV600E /RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors. This observational cohort study combined a population-based Dutch cohort (2014-2019) and a large French multicenter cohort (2007-2017). All mCRC patients with a histologically proven dMMR tumor were included. In our real-world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first-line palliative systemic chemotherapy. Mean age of first-line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66-1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67-1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64-1.59), with similar results for PFS. BRAFV600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision-making in dMMR mCRC patients and underline the complex heterogeneity of mCRC.

Soluble urokinase-type plasminogen activator receptor, suPAR, as a prognostic biomarker in advanced pancreatic cancer.

e16277 Background: High levels of intact and cleaved forms of the urokinase-type Plasminogen Activator Receptor (uPAR) in tissue and blood are associated with a poor prognosis in several types of cancer, including lung, colon, bladder, and cholangiocarcinoma. The soluble forms of uPAR (suPAR) have not been investigated in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to determine if circulating levels of intact and cleaved suPAR were associated with overall survival (OS) in patients with advanced PDAC. Methods: Patients with PDAC stage 3 or 4 were consecutively included in the BIOPAC study (ClinicalTrials.gov ID: NCT03311776) in a training cohort (n = 230, age 45-89 years, 56% females) from Herlev Hospital and a validation cohort (n = 115, age 40-82 years, 59% females) from four other Danish hospitals between 2008 to 2014. A total of 95% of the patients in the training cohort and 93% in the validation cohort received first-line palliative chemotherapy. One patient was alive at the time of analysis at 8 years follow-up. Serum samples were collected prior to palliative chemotherapy. Different suPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for uni- and multivariate analyses. Age, performance status, stage (4 vs 3), gender, Charlson age-adjusted comorbidity index, and CA19-9 were included in the multivariate analysis for OS. Results: In the training cohort, high level of suPAR domain I was an independent biomarker of short OS (HR, 1.37, 95% CI 1.15-1.63, p = 0.0004). High CA19-9 (HR, 1.08, 95% CI 1.04-1.12, p &lt; 0.0001), PS, and stage were also independent prognostic parameters in the training cohort. In the validation cohort, high level of suPAR domain I (HR, 1.91, 95% CI 1.36-2.69, p = 0.0002) and CA 19-9 (HR, 1.09, 95% CI 1.01-1.17, p = 0.02) were confirmed as independent prognostic biomarkers for short OS. No correlation was observed between suPAR domain 1 and CA19-9 (r = 0.059, p = 0.21). Conclusions: A high pretreatment circulating level of suPAR domain I is associated with a short OS in patients with advanced PDAC, and the biomarker is independent of CA19-9. The results warrant further investigation of suPAR domain 1 as a biomarker in patients with PDAC.

Comparison of prophylactic effects for chemotherapy induced neutropenia between same-day versus next-day administration of pegteograstim (Neurapeg®) in patients treated with chemotherapy regimen composed of day 1 intensive myleosuppressive agent: A randomized phase III clinical trial.

Administration of pegylated granulocyte-colony-stimulating factor (peg-GCSF) 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of grade (Gr) 4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day method in preventing CIN, especially in chemotherapy regimens that include day 1 myelosuppressive agents. Thus, we aim to verify the hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or first-line palliative chemotherapy comprising intensively myelosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. The randomizations are stratified according to number of patient CIN risk factors (1 vs ≥2), chemotherapy setting (perioperative vs palliative), and interval (2-week vs 3-week). In the same-day arm, pegteograstim 6 mg is subcutaneously injected within 4 hours after completion of chemotherapy. In the next-day arm, pegetograstim is injected at 24 to 36 hours post-chemotherapy. A complete blood count test is performed daily from day 5 to 9 during the cycle 1. The primary endpoint is duration of Gr4 CIN (cycle 1), and secondary endpoints include incidence of Gr 3 to 4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery absolute neutrophil count 1000/μL (cycle 1), incidence of febrile neutropenia, incidence of CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each group.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Sex and gender differences in treatment intention, quality of life and performance status in the first 100 patients with periampullary cancer enrolled in the CHAMP study

BackgroundPeriampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3rd leading cause of cancer death for both sexes and while surgery is the only option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial.MethodsThe study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan–Meier analysis.ResultsThere was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline.ConclusionsThis study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes.Trial registrationNCT03724994.

Priapism in a Patient with Rectal Adenocarcinoma

Priapism is a very rare complication of malignancy and is usually accompanied by locally advanced or widely metastatic disease. We describe a case of priapism arising in a 46-year-old male with localised rectal cancer that was responding to therapy. This patient had just completed two weeks of neoadjuvant, long-course chemoradiation when he presented with persistent painful penile erection. Assessment and diagnosis were delayed for more than 60 h, and although a cause could not be determined from imaging, a near complete radiological response of the primary rectal cancer was seen. His symptoms were refractory to urologic intervention and were associated with extreme psychological distress. He re-presented shortly thereafter with extensively metastatic disease in the lungs, liver, pelvis, scrotum, and penis; additionally, multiple venous thromboses were identified, including in the dorsal penile veins. His priapism was not reversible and was associated with a considerable symptom burden for the remainder of his life. His malignancy did not respond to first-line palliative chemotherapy or radiation, and his clinical course was further complicated by obstructive nephropathy, ileus, and genital skin breakdown with a suspected infection. We initiated comfort measures, and he ultimately died in hospital less than five months after his initial presentation. Priapism in cancer is usually related to tumour infiltration of the penis and corporal bodies resulting in poor venous and lymphatic drainage. The management is palliative and can include chemotherapy, radiation, surgical shunting, and potentially penectomy; however, conservative penis-sparing therapy may be reasonable in patients with limited life expectancy.

Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy.

Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy.

Prognostic value of baseline functional status measures and geriatric screening in vulnerable older patients with metastatic colorectal cancer receiving palliative chemotherapy – The randomized NORDIC9-study

IntroductionAppropriate patient selection based on functional status is crucial when considering older adults for palliative chemotherapy. This pre-planned analysis of the randomized NORDIC9-study explored the prognostic value of four functional status measures regarding progression-free survival (PFS) and overall survival (OS) in vulnerable older patients with metastatic colorectal cancer (mCRC) receiving first-line palliative chemotherapy. Materials and methodsPatients ≥70 years of age with mCRC not candidates for standard full-dose combination chemotherapy were randomized to receive full-dose S1 or reduced-dose S1 + oxaliplatin. At baseline, functional status was assessed using ECOG performance status (ECOG PS), frailty phenotype, Geriatric 8 (G8), and Vulnerable Elderly Survey-13 (VES-13). Multivariable regression models were applied and C-statistics were estimated. ResultsIn total, 160 patients with a median age of 78 years (IQR: 76–81) were included. While in univariate analyses, ECOG PS, frailty phenotype, and VES-13 were statistically significantly associated with differences in OS between subgroups, G8 was not (HR = 1.55, 95%CI: 0.99–2.41, p = 0.050). In multivariable analyses adjusted for age, sex, body mass index, and treatment allocation, we found significant differences between subgroups for all applied tools and with C-statistics in the moderate range for ECOG PS and VES-13.Concerning PFS, statistically significant differences were observed between subgroups of ECOG PS, G8, and VES-13 both in uni- and multivariable analyses, but not for frailty phenotype. DiscussionIn this Nordic cohort of vulnerable older patients with mCRC, baseline ECOG PS, frailty phenotype, G8, and VES-13 showed prognostic value regarding overall survival, and moderate predictive value of models based on ECOG PS and VES-13 was demonstrated.

Enhanced supportive care for advanced cancer patients: study protocol for a randomized controlled trial

BackgroundEarly palliative care along with standard cancer treatments is recommended in current clinical guidelines to improve the quality of life and survival of cancer patients. This study protocol aims to evaluate the effect of “Enhanced Supportive Care”, an early primary palliative care provided by nurses.MethodsA randomized controlled trial (RCT) will be conducted including advanced cancer patients scheduled for first-line palliative chemotherapy (N=360) and their caregivers in South Korea. Participants will be randomly assigned to the intervention or control group in a 1:1 ratio. Participants in the intervention group will receive the “Enhanced Supportive Care”, which provides five sessions of symptom management and coping enhancement counseling by nurses. The control group will receive symptom monitoring five times. The primary endpoints are symptoms, coping, and quality of life (QoL) at 3 months. Secondary endpoints are symptoms, coping, and QoL at 6 months, depression and self-efficacy for coping with cancer at 3 and 6 months, symptom and depression change from baseline to 3 months, survival at 6 and 12 months among patients, and depression among caregivers at 3 and 6 months.DiscussionThis RCT will evaluate the effects of “Enhanced Supportive Care” on symptoms, depression, coping, self-efficacy for coping with cancer, QoL and survival of patients, as well as depression of caregivers. It will provide evidence of a strategy to implement early primary palliative care provided by nurses, which may consequently improve cancer care for newly diagnosed patients with advanced stage cancer.Trial registrationClinicalTrials.gov, NCT04407013. Registered on May 29, 2020, https://www.clinicaltrials.gov/ct2/show/study/NCT04407013. The protocol version is ESC 1.0.

Abdominal adiposity as a prognosis biomarker of clinical outcome in metastatic colorectal cancer

ObjectivesAdipose tissue distribution and radiodensity are associated with prognosis in many types of cancer. However, the roles of adipose tissue distribution and radiodensity in patients with metastatic colorectal cancer (mCRC) remain unclear. The aim of this study was to assess the prognostic effect of adiposity and adipose tissue radiodensities in patients with mCRC. MethodsPatients with mCRC who received first-line palliative chemotherapy and had a computed tomography (CT) scan at the third lumbar vertebra (L3) level, admitted between January 2010 and December 2018, were sequentially enrolled. Body composition was assessed using CT-derived measurements. Univariate and multivariate logistic regression analyses and Kaplan–Meier curves were used to determine prognostic values. ResultsThe study included 237 patients. Cox analyses demonstrated that high subcutaneous adipose tissue (SAT) index was associated with a lower risk for death (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29–0.88; Ptrend < 0.025). There was no significant association between visceral adipose tissue (VAT) index tertiles and overall survival. However, high VAT and SAT radiodensities were significantly associated with increased mortality (HR, 1.80; 95% CI, 1.12–2.89; Ptrend < 0.030 and HR, 1.85; 95% CI, 1.19–2.86; Ptrend < 0.021, respectively). ConclusionsA higher SAT index in patients with mCRC was associated with a favorable overall survival outcome, whereas higher SAT and VAT radiodensities were associated with an increased risk for death, supporting that early nutritional intervention may improve mCRC prognosis.