Significant Overall Survival Benefit Research Articles

Impact of prior nivolumab use on the efficacy of second-line taxane-based chemotherapy in advanced gastric or esophagogastric junction adenocarcinoma.

352 Background: Taxane-based chemotherapy remains the standard second-line treatment after first-line treatment including anti-PD-1 antibody therapy for patients with advanced gastric or esophagogastric junction adenocarcinoma (GA/EGA). The CheckMate 649 trial suggested that prior use of nivolumab in the first-line setting was associated with longer progression-free survival (PFS) with subsequent treatment. However, there have been few reports on the difference in efficacy of taxane-based chemotherapy as second-line treatment with or without prior nivolumab use in the real-world setting. Methods: We retrospectively reviewed the medical records of patients with advanced GA/EGA who received solvent-based paclitaxel or nanoparticle albumin–bound (nab)-paclitaxel chemotherapy regimens as second-line treatment after first-line platinum-based chemotherapy between January 2018 and August 2024. We divided the patients into two groups: those who received nivolumab with the first-line chemotherapy (Nivo group) and those who did not (non-Nivo group). PFS and overall survival (OS) were estimated using the Kaplan–Meier method and compared between the two groups using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated by univariate and multivariate Cox regression analysis. Results: A total of 115 patients were included: 27 patients in the Nivo group and 88 in the non-Nivo group. Patient backgrounds did not differ significantly in terms of age (median 67/67 years), sex (male 59%/57%), performance status (PS; ≥2 11%/15%), site of primary tumor (EGA 11%/9%), number of metastatic sites (≥3 33%/18%), and ramucirumab use (yes 82%/82%). For the taxane regimens, nab-paclitaxel-based treatment was significantly more common in the non-Nivo group (11.1% /55.7%, p<0.001). There was a tendency toward longer PFS in the Nivo group compared with the non-Nivo group (median 4.2 months [95%CI 2.8-6.0] vs. 2.3 months [95%CI 2.0-3.0], HR 0.65 [95%CI 0.40-1.03]; p=0.067.) The objective response rate was numerically higher in the Nivo group compared with the non-Nivo group (29.4% vs. 17.6%, p=0.315). OS was not significantly different between the Nivo and non-Nivo groups (median 9.6 months [95%CI 4.9-NA] vs. 6.6 months [95%CI 5.5-10.8], HR 0.92 [95%CI 0.52-1.64]; p=0.785). In the non-Nivo group, 64 patients (73%) received subsequent chemotherapy, and 63 patients (72%) received nivolumab. Multivariate analysis identified prior use of nivolumab was a favorable prognostic factor for PFS (HR 0.55 [95%CI 0.31-0.97]; p=0.039). However, prior use of nivolumab did not show a significant benefit for OS (HR 1.09 [95% CI: 0.56-2.13]; p = 0.802). Conclusions: Prior use of nivolumab in first-line platinum-based chemotherapy had a positive impact on PFS with taxane-based second-line chemotherapy in advanced GA/EGA.

Can overall survival (OS) benefit be predicted from improvements in progression-free survival (PFS) for previously untreated metastatic colorectal cancer (mCRC)?

222 Background: With improvements in treatment of mCRC, OS maintains its gold standard efficacy measure but takes longer to mature than intermediate endpoints. This study analyzed the association between treatment effects on PFS and OS using aggregate-level data from RCTs in previously untreated mCRC patients. Methods: A systematic literature review identified RCTs in previously untreated mCRC patients published from 2010–2021 reporting hazard ratios on PFS (HR PFS ) and OS (HR OS ). All treatments in comparison to chemotherapy alone or chemotherapy with anti-VEGF (bevacizumab) or anti-EGFR (cetuximab) targeted therapy were considered. Correlation between HR PFS and HR OS was evaluated using bivariate random-effects meta-analysis (BRMA) and weighted linear regression (WLR). Predictive performance of the surrogacy equations from WLR was assessed using leave-one-out cross-validation (LOOCV). Surrogate threshold effects (STE), defined as the minimum PFS benefit that would translate into a statistically significant OS benefit with 95% probability, were also derived to gauge the practical utility of the models. Primary analysis consisted of all included trials. Sensitivity analyses omitted trials that (I) had anti-EGFR medications, (II) had anti-VEGF medications, (III) violated proportional hazards assumptions, and (IV) permitted treatment crossover. Results: In the primary analysis 47 trials were included. The estimated correlation between PFS and OS was 0.67 (95% CI: 0.48–0.80) using BRMA and 0.70 (95% CI: 0.48–0.84) using WLR. The surrogacy equation derived from WLR was log(HR OS ) = −0.03 + 0.56 log(HR PFS ) with a statistically insignificant intercept and significant slope. Estimated STEs corresponding to sample sizes of 200 and 300 patients were 0.55 and 0.62, respectively. Observed HR OS ’s were within their 95% prediction intervals predicted from HR PFS for 93.6% of studies in LOOCV. Sensitivity analyses produced moderate correlations with >90% coverage in LOOCV (Table). Conclusions: Moderate correlations were found between HR PFS and HR OS using both modeling approaches, highlighting the stability of the findings. Cross-validations of surrogacy equations indicated promising predictive value of PFS benefit for OS benefit in previously untreated mCRC. Analysis Set​ # of Studies​ Correlation (95% CI) STE LOOCV​Coverage Rate​ BRMA WLR N = 200 N = 300 Sensitivity Analysis I​ 34​ 0.75 ​(0.57, 0.86)​ 0.78 ​(0.55, 0.90)​ 0.55​ 0.61​ 94.1​% Sensitivity Analysis II​ 14​ 0.44 ​(-0.08, 0.77)​ 0.62 ​(-0.05, 0.90)​ 0.44​ 0.52​ 92.9​% Sensitivity Analysis III​ 36​ 0.61 ​(0.36, 0.77)​ 0.59 ​(0.26, 0.80)​ 0.46​ 0.55​ 94.4​% Sensitivity Analysis IV 43​ 0.68 ​(0.48, 0.81)​ 0.67​(0.41, 0.83)​ 0.52​ 0.60​ 93.0​%

Efficacy of radiotherapy in treating local recurrence concomitant with distant metastasis of nasopharyngeal carcinoma: a long-term retrospective multicenter study.

Patients with nasopharyngeal carcinoma (NPC) experiencing locoregional recurrence concomitant with distant metastases (rmNPC) after initial treatment represent a unique subgroup with significant management challenges. This study aimed to evaluate overall survival (OS) in rmNPC patients treated with systemic therapies with or without radiotherapy. This retrospective multicenter study included patients with locally recurrent and metastatic NPC from five hospitals. Kaplan-Meier analyses and log-rank tests were applied to assess survival outcomes based on recurrence and metastasis profiles, as well as treatment modalities. Independent prognostic factors affecting OS were identified using Cox regression models. A total of 52 patients were analyzed, with a median follow-up duration of 68.3 months (range: 7-240 months). The median OS was 23.4 months (range: 11.1-35.6 months), and the 1-, 2-, 3-, 4-, and 5-year OS rates were 61.3%, 46.5%, 31.0%, 27.9%, and 10.5%, respectively. The treatment modality did not significantly affect OS overall (P = 0.071). Median OS was 10.8 months (95% CI, 7.7-13.9) for chemotherapy alone, 24.2 months (95% CI, 8.9-39.4) for chemotherapy combined with PD-1 inhibitors, and 47.1 months (95% CI, 10.2-84.0) for chemotherapy combined with radiotherapy. In patients with oligometastasis, radiotherapy significantly improved OS (50.1 vs. 24.1 months, P = 0.021), whereas no significant OS benefit was observed for radiotherapy in polymetastatic patients (8.6 vs. 14.8 months, P = 0.168). Similarly, radiotherapy extended OS in patients with one-organ metastases (50.1 vs. 24.1 months, P = 0.026), while no significant benefit was observed in those with multiple-organ metastases (8.6 vs. 11.0 months, P = 0.831). Radiotherapy, when combined with other treatment modalities, significantly improves OS in rmNPC patients with oligometastases or one-organ metastases.

The efficacy of second-line chemotherapy for advanced biliary tract cancer: A systematic review and network meta-analysis.

This network meta-analysis (NMA) aims to provide evidence-based guidance for selecting the second-line chemotherapy for biliary tract cancer (BTC). A comprehensive literature search was conducted on PubMed, Cochrane, and EMBASE through July 2024. Inclusion criteria involved: (1) patients underwent second-line chemotherapy following platinum-based first-line therapy, (2) intervention/comparator groups consisted of various chemotherapeutic agents, and (3) outcomes measured as hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) in randomized controlled trials (RCTs) and cohort studies. Outcomes were measured as HR of OS and PFS in RCTs and cohort studies. The eight studies consisting of 1621 patients were selected. In the NMA for OS, 5FU_plus_Plat (fluorouracil plus oxaliplatin or cisplatin; HR 0.52, 95% confidence interval [CI]: 0.30-0.91), nal-IRI_5FU_LV (nano-liposomal irinotecan plus fluorouracil and LV; HR 0.54 [95% CI: 0.32-0.92]), and FOLFOX (fluorouracil plus oxaliplatin; HR 0.69 [95% CI: 0.50-0.96]) demonstrated significant benefits in OS when compared to control. For PFS, nal-IRI_5FU_LV (HR 0.61 [95% CI: 0.44-0.85]) provided a significant advantage over 5FU. Second-line chemotherapy for BTC after the failure of gemcitabine plus platinum as first-line therapy, nal-IRI_5FU_LV appears to be the most promising second-line therapy in terms of both OS and PFS.

Impact of Immunotherapy on the Care Patterns and Outcomes of Patients with Advanced Hepatocellular Carcinoma.

Modern immunotherapy with checkpoint inhibitors revolutionized cancer treatment and outcomes. This study aims to demonstrate how immunotherapy has impacted the national landscape of systemic treatment and palliative care in advanced hepatocellular carcinoma (HCC). Retrospective cohort selecting patients from the U.S.-based National Cancer Database (NCDB) with clinical stages T3b/T4 and stage IV HCC from 2010 to 2021. We performed a multivariable analysis using the Cox proportional hazard for overall survival (OS) comparisons and a logistic regression model to study immunotherapy use. Immunotherapy use increased from 0.27% in 2010 to 33.80% in 2021. The median OS survival (in months) was 2 for untreated patients, 7.20 for chemotherapy, and 7.46 for immunotherapy. There was a better OS with immunotherapy (HR 0.59, 95% CI 0.56-0.62). Systemic therapy for palliation increased from 14.41% in 2010 to 25.32% in 2021. Compared to surgical palliation, radiation (HR 0.61, 95% CI 0.52-0.71) and systemic palliative (HR 0.59, 95% CI 0.51-0.69) therapies improved OS. From 2010 to 2021, there was a significant increase in the use of immunotherapy, parallel to a large shift toward systemic therapy use for palliative care in patients with advanced HCC. Immunotherapy was associated with a significant OS benefit in the palliative setting.

Quantitative evaluation of the efficacy and safety of first-line systemic therapies for advanced hepatocellular carcinoma.

This study aimed to quantitatively evaluate the efficacy and safety of first-line systemic therapies for treating advanced hepatocellular carcinoma (aHCC). The study included clinical trials of first-line systemic therapies for aHCC since the approval of sorafenib in 2007. Hazard function models were used to describe changes in overall survival (OS) and progression-free survival (PFS) over time. Monte Carlo simulation was used to compare OS and PFS for different treatments, including sorafenib, antiangiogenic therapies (AATs) (except sorafenib), immune checkpoint inhibitor (ICI) monotherapy, AAT + targeted therapy, AAT + chemotherapy, AAT + ICIs, and ICIs + ICIs. Furthermore, the objective response rate (ORR) and incidence of grade ≥ 3 adverse events were analyzed. Fifty studies comprising 12,918 participants were included. AAT + ICIs demonstrated a significant benefit in median OS (mOS), median PFS (mPFS), and ORR (20.5 [95% CI 17.5-24] months, 7.5 [95% CI 6.5-8.8] months, and 24% [95% CI 17%-30%], respectively). ICIs + ICIs and ICI monotherapy ranked second and third, respectively with an mOS of 20 (95% CI 18.5-21.5) months and 14.5 (95% CI 13.5-16) months, respectively. The OS, PFS, and ORR of patients treated with AAT, AAT + targeted therapy, and AAT + chemotherapy were similar to those of patients treated with sorafenib. A higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage C had a shorter OS. OS was associated with publication year, and PFS was associated with the proportion of patients with BCLC stage C. The incidence of grade ≥ 3 adverse events in the ICIs and ICIs + ICIs treatment groups was low. The study results provide valuable information from which to base rational clinical drug use and serves as a reliable external control for evaluating new treatments for aHCC.

Secondary cytoreductive surgery in platinum-sensitive relapsed ovarian cancer: a meta-analysis of randomized controlled trials.

To evaluate the role of secondary cytoreduction in patients with platinum-sensitive recurrent ovarian cancer. The PubMed, Medline, Embase, Cochrane Library and Web of Science databases were searched. Randomized controlled trials (RCTs) that compare secondary cytoreduction plus chemotherapy with chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer were selected. Pooled hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. There was no difference in overall survival (OS) between the surgery group and no surgery group (HR = 0.89; 95% CI 0.77, 1.04; p = 0.14), but secondary cytoreduction showed a significant improvement in progression-free survival (PFS) (HR = 0.67; 95% CI 0.54, 0.76; p < 0.00001). A subgroup analysis comparing the complete gross resection subpopulation with the no surgery group achieved a significant longer OS (HR = 0.70, 95% CI 0.58-0.85; p = 0.0003) and a greater PFS benefit (HR = 0.56, 95% CI 0.48-0.66; p < 0.00001). In addition, as compared with incomplete resection, the OS benefit of complete gross resection was more evident (HR = 0.51, 95% CI 0.37-0.69; p < 0.0001). In women with platinum-sensitive recurrent ovarian cancer, although secondary cytoreduction followed by chemotherapy resulted in longer PFS than chemotherapy alone, it did not lead to significant benefit in OS. However, when complete gross resection was achieved, it significantly prolonged OS and provided a greater PFS benefit.

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322). Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing. Multivariate analysis was performed. A p-value of 0.05 was considered significant. Progression-free survival (PFS) and overall survival (OS) were compared between groups defined by ctDNA kinetic profile. Cox survival model was used to search variables associated with PFS and OS. Kaplan-Mayer curve was used to graphically express the differences in PFS and OS. A log-rank test compared the two curves. 188 patients were included. Blood samples were available for 168 patients at T0 and for 160 patients at T0 and T1 to assess ctDNA ratio kinetics. At T0, 107 patients (63.7%) had detectable ctDNA. At T1, 137 (85.6%) patients had negative ctDNA or a decrease of more than 80%. There was a significant benefit in either PFS (p=0.0017) or OS (p=0.0036) in favor of early decrease of ctDNA ratio. A favorable decrease was associated with a greater likelihood of being able to perform CRS (OR: 3.94 (CI95% 1.45-10.70), p=0.0074). Early decrease of ctDNA ratio can provide prognostic information early in the management of patients, allowing a more accurate information to patients and an early preparation for CRS (prehabilitation).

Nomograms for predicting the prognosis in multiple primary esophageal squamous cell carcinoma

Background Due to its rarity, it is challenging to predict the survival of patients with synchronous multiple primary esophageal squamous carcinomas (SMPESCs). We aimed to construct nomograms to predict survival outcomes and help to make therapeutic strategy for patients with SMPESCs. Materials and Methods The clinical and survival data of 135 patients with SMPESCs were analyzed retrospectively. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. Nomograms were constructed to predict 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS). In addition, we further evaluated the effect of postoperative adjuvant therapy on SMPESCs patients with lymph node metastasis. Results In univariate and multivariate analyses of DFS and OS, age, site of the main lesion, lymph node metastasis, total number of lymph nodes dissected, lactate dehydrogenase level and lymphocyte-to-monocyte ratio were identified as independent prognostic factors. These characteristics were further included to establish nomograms. For the internal validation of the nomogram predictions of survival outcomes, the concordance indices were 0.752 and 0.756, respectively. Decision curve analysis also proved the efficacy of the nomograms. Furthermore, adjuvant therapy had a statistically significant benefit for OS but not DFS in patients with lymph node metastasis. Conclusions These nomograms could effectively predict the 1-year, 3-year and 5-year survival outcomes of patients with SMPESCs. Furthermore, adjuvant therapy has the potential to improve OS in patients with lymph node metastasis.

Novel hormonal agents in men with metastatic castration resistant prostate cancer and reduced performance status: Experiences of a specialized single center.

Attaining castration resistance in metastatic prostate cancer (mCRPC) represents a pivotal juncture in the progression of the patient's illness and treatment regimen. Within this therapeutic context, novel hormonal agents (NHA) constitute a fundamental component of pharmacological intervention. However, the efficacy of NHA therapy remains uncertain for patients with a compromised general condition, as indicated by an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≥2. Notably, most clinical trials excluded individuals with an ECOG PS ≥2, leaving a gap in our understanding of the potential benefits of NHA therapy for this specific patient cohort. We conducted an analysis of fifty-three NHA-naïve men characterized by attaining mCRPC at an ECOG PS of ≥2 subsequent to androgen deprivation monotherapy between 2008 and 2023. Patients were then treated with either NHA or Best Supportive Care (BSC) based on individual decisions. Survival and adverse event (AE) analysis was performed to assess the outcomes of NHA therapy compared to BSC. Among the patients, 30 (56.6%) received NHA, whereas the remaining 23 (43.4%) choose BSC. No significant differences in baseline characteristics were observed between the NHA and BSC group. Median overall survival (OS) was 9.1 months in the BSC group and 7.0 months in the NHA group, with no significant OS benefits associated with NHA treatment. AEs and severe AEs commonly occurred, but remained indifferent between treatment groups. Our findings suggest that NHA therapy may confer reduced survival benefits in mCRPC patients with ECOG PS ≥2. While hope for NHA treatment persists, particularly given its oral administration and tolerability, careful consideration and discussion with patients regarding treatment expectations and palliative care goals are warranted in this challenging patient population.

Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting.

S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy. The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates. A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50months (95% CI 4.18-12.69months) in the nal-IRI + 5-FU/LV group and 5.72months (95% CI 2.76-10.79months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399-0.941; p = 0.025). These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy.

Optimal hyperthermic intraperitoneal chemotherapy regimen for advanced and peritoneal metastatic gastric cancer: a systematic review and Bayesian network meta-analysis.

Peritoneal metastasis is one of the most common modes of spread of gastric cancer. Currently, surgical treatment combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic chemotherapy has demonstrated promising outcomes in both the treatment and prevention of peritoneal metastasis in gastric cancer. However, various HIPEC drug regimens are in clinical use, and their efficacy remains unclear. This study aims to evaluate the effectiveness of different HIPEC drug regimens in patients with advanced gastric cancer to determine the optimal therapeutic approach. This study conducted a systematic review and Bayesian network meta-analysis. Patients in the experimental group underwent surgery combined with HIPEC and chemotherapy. The search period covered literature from database inception to June 1, 2024. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate overall survival (OS) as the primary outcome. Odds ratios (ORs) with 95% CIs were used to assess overall disease recurrence, peritoneal recurrence, and postoperative morbidity as secondary outcomes. To ensure scientific rigor and transparency, this study has been registered with PROSPERO (CRD42024533948). A total of 11 randomized controlled trials (RCTs) involving 1092 patients were included. Compared to surgery combined with chemotherapy, the regimens of cisplatin (HRs = 0.52, 95% CI: 0.38-0.73), mitomycin C (HRs = 0.99, 95% CI: 0.55-1.79), cisplatin plus fluorouracil (HRs = 0.60, 95% CI: 0.38-0.95), and oxaliplatin plus 5-fluorouracil (HRs = 0.53, 95% CI: 0.36-0.78) all demonstrated benefits in OS. The cisplatin (ORs = 0.16, 95% CI: 0.03-0.60) and mitomycin C (ORs = 0.03, 95% CI: 0-0.71) regimens also showed advantages in reducing peritoneal recurrence, with no impact on postoperative morbidity. Importantly, the cisplatin regimen was superior to other regimens in terms of OS and overall disease recurrence, achieving a balance between efficacy and safety. Compared to chemotherapy alone, HIPEC treatment shows significant benefits in OS without a notable disadvantage in postoperative morbidity. Although no single HIPEC regimen demonstrated clear benefits across all outcomes, the cisplatin regimen performed well in multiple aspects, indicating its potential for further research and clinical application. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=533948, identifier CRD42024533948.

The role of chemotherapy in the management of pancreatic acinar cell carcinoma.

Pancreatic acinar cell carcinoma (pACC) is a rare malignancy with unique clinical and molecular features. The role of chemotherapy in pACC management is not well established. The National Cancer Database (NCDB) for pACC was used. Cox regression was used in resected pACC patients to identify significant overall survival (OS) predictors. Patients were then divided based on these risk factors into propensity-matched group of surgery versus surgery + chemotherapy and Kaplan-Meier analysis was performed with log-rank tests to compare OS. The NCDB 2004-2020 included 1592 pACC patients, 1553 were selected. Median age was 66 and 1090 (70.2%) were males. 622 (40.1%) received chemotherapy only, 257 (16.5%) had surgery only, and 365 (23.5%) had both. 189 Patients who received surgery were only matched to peers who had surgery + chemotherapy. The median OS for surgery only was 57.8 ± 6.0 versus 54.2 ± 9.9 months for surgery + chemotherapy (p = 0.836). Cox regression identified nodal and margin status as independent predictors of OS. Therefore, subgroups of patients with node-negative, node-positive, margin-negative, and margin-positive resections were similarly matched 1:1 for the receipt of surgery only versus surgery + chemotherapy. Only patients with node-positive disease had a significant OS benefit with the addition of chemotherapy (44.2 ± 7.3 vs. 27.5 ± 10.5 months; p = 0.036). Our analysis suggests that surgical resection remains the cornerstone of therapy for pACC. Node status and margin status are the primary prognosticators. The addition of chemotherapy provides an OS benefit only in node-positive disease.

Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) – A phase 3 randomized controlled trial

PurposeRadiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients. Materials and MethodsNon-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43. ResultsFrom April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression. ConclusionThis is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation.

Long-Term Outcome After Resection of Hepatic and Pulmonary Metastases in Multivisceral Colorectal Cancer.

Colorectal cancer (CRC) with hepatic (CRLM) and pulmonary metastases (CRLU) presents a significant clinical challenge, leading to poor prognosis. Surgical resection of these metastases remains controversial because of limited evidence supporting its long-term benefits. To evaluate the impact of surgical resection of both hepatic and pulmonary metastases on long-term survival in patients with multivisceral metastatic colorectal cancer, this retrospective cohort study included 192 patients with UICC stage IV CRC treated at a high-volume academic center. Patients were divided into two groups: those who underwent surgical resection of both hepatic and pulmonary metastases (n = 100) and those who received non-surgical treatment (n = 92). Propensity score matching was used to adjust for baseline differences. The primary outcome was overall survival (OS). Unadjusted analysis showed a significant OS benefit in the surgical group (median OS: 6.97 years) compared with the conservative group (median OS: 2.17 years). After propensity score matching, this survival advantage persisted (median OS: 5.58 years vs. 2.35 years; HR: 0.3, 95% CI: 0.18-0.47, p < 0.0001). Surgical resection of hepatic and pulmonary metastases in multivisceral metastatic CRC significantly improves long-term survival, supporting an aggressive surgical approach in selected patients.

The repeated treatment of targeted therapy in the treatment of skin melanoma

Currently, patients with disseminated forms of skin melanoma have limited treatment options. The most effective treatments, according to research, are targeted drugs BRAF/MEK inhibitors when a mutation in exon 15 of the BRAF gene is detected in tumor biopsy tissue and immune synapse modulators, specifically anti-CTLA-4 and anti-PD-1 drugs. Both classes of drugs show a significant benefit in overall and progression-free survival, but convincing data on their effectiveness in second and subsequent lines of therapy are still lacking. Most often, with the progression of disseminated skin melanoma during tyrosine kinase inhibitor therapy, a dual immunotherapy combination is used. In the event of further progression, due to the limited treatment options, clinical oncologists face questions about the possibility of returning to targeted therapy, changing tyrosine kinase inhibitor drugs, or using the initial combination, and their impact on progression-free survival in choosing treatment strategies for such patients, as well as the potential use of BRAF/MEK inhibitors. Assessing the reuse of tyrosine kinase inhibitor drugs is a highly relevant issue in clinical oncology.

Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival.

Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 109/L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 109/L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00-0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781.

Regorafenib monotherapy as the later-line treatment for elderly patients with metastatic colorectal cancer: a multicenter real-world study.

Colorectal cancer is one of the tumors with the highest morbidity and mortality rates in China and the world. Regorafenib is a targeted drug for standard third-line treatment of metastatic colorectal cancer (mCRC). Regorafenib monotherapy has shown certain efficacy in the elderly population, but more robust evidence is needed. The aim of this study was to evaluate the dosing characteristics, prognosis, and safety of regorafenib monotherapy in elderly Chinese patients with mCRC. This retrospective study comprised elderly patients (aged ≥60 years) with mCRC who received regorafenib monotherapy as a third-line or above treatment in 10 hospitals from August 2017 to June 2020. We analyzed the association between different dosing regimens and prognosis. The primary endpoint was overall survival (OS), and other endpoints included progression-free survival (PFS) and adverse events (AEs). In total, 203 patients were included in the analysis. The median PFS was 3.88 months [95% confidence interval (CI): 3.48-5.65], and the median OS was 10.1 months (95% CI: 8.94-12.1). There was no significant difference in the survival curves between the different dosage groups. The multivariate Cox analysis showed a significant benefit in OS in the high final daily dose group (120-160 mg/day) [hazard ratio (HR): 0.45, 95% CI: 0.25-0.84, P=0.01], which was further confirmed by the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis. No significant association was found between the initial daily dose and prognosis. Nor was any significant association found between PFS and drug dosage. Subsequently, an age subgroup analysis was conducted using 70 years as the cut-off value. In those aged <70 years, the application of higher final doses (120-160 mg/day) was significantly associated with the prolongation of OS compared to a final dose of 80 mg/day [HR (95% CI): 0.38 (0.16-0.91), P=0.03], and the prolongation of OS was predominantly observed in the 120 mg/day dose group [HR (95% CI): 0.24 (0.09-0.67), P=0.006]. Besides, we observed a statistically insignificant increase in the incidence of AEs in the higher dose group compared to the lower dose group. Regorafenib monotherapy was shown to be efficacious in the elderly population, but further evidence is needed for guidance. Based on our multicenter real-world investigation, the final daily dose was significantly associated with OS. For those aged <70 years, maintaining the final dose at 120 mg/day may have prognostic advantages. The suggested medication protocol requires validation through comprehensive clinical trials.

Molecular Profile as an Outcome Predictor in Glioblastoma along with MRI Features and Surgical Resection: A Scoping Review.

Glioblastoma (GBM) is one of the most aggressive malignant tumors of the brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze the most important outcome predictors in patients with GBM and to compare these factors in terms of absolute months of survival benefit and percentages. Performing a gross total resection for patients with GBM undergoing optimal chemo- and radiotherapy provides a significant benefit in overall survival compared to those patients who received a subtotal or partial resection. However, compared to IDH-Wildtype GBMs, patients with IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status is another strong outcome predictor for patients with GBM. In the reviewed literature, patients with methylated MGMT promoter lived approximately 50% to 90% longer than those with an unmethylated MGMT gene promoter. Moreover, KPS is an important predictor of survival and quality of life, demonstrating that we should refrain from aggressive surgery in important brain areas. As new therapies (such as TTFs) emerge, we are optimistic that the overall median survival will increase, even for IDH-Wildtype GBMs. In conclusion, molecular profiles are stronger outcome predictors than the extent of neurosurgical resection for GBM.

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials

BackgroundThe comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. MethodsProspective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. ResultsA total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67–0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9–67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64–0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65–0.92, p=0.004) and 0.79 (95 % CI: 0.65–0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. ConclusionsOur findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.