Tandem high-dose therapy in relapsed and refractory B-cell lymphoma: results of a prospective phase II trial of myeloablative chemotherapy,followed by escalated radioimmunotherapy with <Superscript>131</Superscript>I-anti-CD20 antibody and stem cell rescue

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with ¹³¹I-anti-CD20 antibody (¹³¹I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2–6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with ¹³¹I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.     

MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer

BackgroundLow miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva).MethodsSeventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n = 43) or Beva (n = 29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT).ResultsBRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases.ConclusionIn this study, miR-31-3p couldn't identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.     

Correlation between efficacy endpoints in patients with advanced biliary tract cancer treated by systemic second-line therapies: Analysis of aggregated data from a systematic literature review

BackgroundOverall response rate (ORR) and progression-free survival (PFS) are commonly used as endpoints for phase II trials. However, the ultimate goal is to bring survival benefit for the patients. We aimed to assess the correlation between ORR, median PFS and overall survival (OS) using aggregated data from a systematic review of second-line systemic therapies in advanced biliary tract cancer (BTC) patients.MethodsClinical trials were identified using Medline database. Studies only enrolling patients with gallbladder cancer were not included. Searches were last updated on April 2020. Eligible studies reported OS, PFS and/or ORR data for BTC patients receiving second-line systemic chemotherapy. Pearson weighted correlation was estimated between OS and ORR and between median OS and PFS.ResultsSeventeen studies (N = 912 patients) were selected. There was a strong correlation between median OS/ORR in the overall analysis (r = 0.85; P < 0.0001), both for trials with chemotherapy (r = 0.90; P=0.0152) and targeted therapy (r = 0.84; P = 0.0006). In contrast, the correlation between median OS/PFS, albeit significant in the overall analysis (r = 0.80; P < 0.0001), remained significant only for targeted therapies in the sensitivity analysis (r = 0.83; P = 0.0009).ConclusionsORR seems to be a more interesting intermediate endpoint in BTC in second line for both chemotherapy and targeted therapies, while PFS may be relevant only for targeted therapy trials. Further well-designed studies for surrogacy evaluation should be performed to confirm this observation.     

Primary mediastinal large B-cell lymphoma (PMLBCL) in Chinese patients: clinical characteristics and prognostic factors

Primary mediastinal large B-cell lymphoma (PMLBCL) is a unique clinico-pathological subtype, for which there is no optimal therapy yet. We evaluated clinical characteristics and prognostic factors in 39 consecutive, previously untreated Chinese patients with PMLBCL. The median age was 28 years (range 16–72 years). The majority of patients were stage I/II (23 cases, 59%). Bulky mediastinal mass was present in 18 cases (46%). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 70 and 64%, respectively. Cox regression analysis showed that low serum albumin was an independent prognostic predictor of both OS (P = 0.002) and PFS (P = 0.001). Other prognostic factors for OS were extra-thoracic involvement (P = 0.016) and B symptoms (with borderline significance, P = 0.053). The addition of radiotherapy to chemotherapy seemed to have a favourable impact on OS (P = 0.034) and PFS (P = 0.039). The addition of rituximab to chemotherapy improved the survival trend, but added no significant benefit (OS: 57 vs. 84%, P = 0.287; PFS: 53 vs. 73%, P = 0.371). Our data additionally suggest that low serum albumin is a novel prognostic predictor for PMLBCL, and could be useful in determining treatment options in the clinic.     

Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies

Background

Bevacizumab is frequently combined with 5-fluorouracil-based chemotherapy for patients with metastatic colorectal cancer (mCRC). The relative benefit of bevacizumab in older patients has not been widely studied and is of interest.

Patients and methods

This retrospective analysis used data from three first-line randomized controlled studies and one second-line randomized controlled study of bevacizumab plus chemotherapy in medically fit (Eastern Cooperative Oncology Group performance status 0 or 1) patients with mCRC. Overall survival (OS) and on-treatment progression-free survival (PFS) were assessed in patients aged <65, ≥65, and ≥70 years. Results were compared using unstratified hazard ratios (HRs). Grade 3–5 adverse events were also assessed.

Results

Bevacizumab statistically significantly improved PFS [HR 0.58; 95% confidence interval (CI) 0.49–0.68] and OS (HR 0.85; 95% CI 0.74–0.97) in patients aged ≥65 years; patients aged ≥70 years had similar improvements. Benefits were consistent across the studies, irrespective of setting, bevacizumab dose, or chemotherapy regimen. Increases in thromboembolic events were observed in patients aged ≥65 and ≥70 years in the bevacizumab group compared with the control group, mainly as a result of increases in arterial thromboembolic events. No other substantial age-related increases in grade 3–5 adverse events were observed.

Conclusions

In medically fit older patients, bevacizumab provides similar PFS and OS benefits as in younger patients.     

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis

Background:The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.Methods:According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.Results:The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).Conclusion:Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.     

Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement

The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm³ was the cutoff value. The low MTV group (<220 cm³) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm³) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.     

Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m²) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.     

Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma

The proteasome inhibitor, bortezomib, potentially increases cell sensitivity to chemotherapy. This study was performed to determine the overall response rate (ORR), overall survival (OS), progression‐free survival (PFS) and toxicity of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) compared to CHOP + bortezomib chemotherapy in mantle cell lymphoma (MCL) patients at first relapse. Forty‐six patients were randomly assigned to standard dose CHOP ± bortezomib 1·6 mg/m² given on a 21‐d cycle for up to eight cycles of treatment. Median age was 71 years (CHOP arm) and 69 years (CHOP‐bortezomib arm). Median Eastern Cooperative Oncology Group performance status was 1 (CHOP) and 0 (CHOP‐bortezomib) with 65% and 52%, respectively, having a disease stage of IV. ORR was 47·8% (CHOP) and 82·6% (CHOP‐bortezomib). Complete response rate was 21·7% (CHOP) vs. 34·8% (CHOP‐bortezomib); partial response rate was 26·1% (CHOP) vs. 47·8% (CHOP‐bortezomib). Median OS was 11·8 months (CHOP) and 35·6 months (CHOP‐bortezomib) (P = 0·01, Hazard ratio [HR] 0·37 [95% confidence interval (CI) 0·16–0·83)] and there was a non‐significant improvement in PFS: 8·1 months (CHOP) and 16·5 months (CHOP‐bortezomib) [P = 0·12, HR 0·60 (95% CI 0·31–1·15)]. Severe (≥grade 3) sensory neuropathy was similar in both arms (4·3% CHOP vs. 6·5% CHOP‐bortezomib). We conclude that the addition of bortezomib to CHOP chemotherapy for relapsed MCL significantly improves outcome with a manageable increase in toxicity.     

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80–0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80–0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08–1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91–1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82–1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63–1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.     

Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: still not out of fashion

The role of autologous hematopoietic stem cell transplantation (autoHSCT) in adult acute lymphoblastic leukemia (ALL) is still unclear. We retrospectively analyzed the results of the autoHSCT and maintenance therapy, with oral 6-mercaptopurine and methotrexate, in comparison to conventional-dose chemotherapy in the consolidation treatment of adult ALL and lymphoblastic lymphoma (LBL). The patients, with HLA identical sibling donor, underwent allogeneic transplantation, while the others were treated with autoHSCT and maintenance therapy with oral 6-mercaptopurine and methotrexate, or by conventional-dose chemotherapy (patient’s decision, no autologous hematopoietic stem cells harvest). Sixty consecutive adult patients (median age 35.2 years; range 17.3 to 70.7) with ALL (n = 52), LBL (n = 7), and acute biphenotypic leukemia (n = 1) were treated in our center from 1997 to 2007. Patients treated with chemotherapy alone (n = 35) had a shorter median progression-free survival (PFS) compared to patients who underwent autoHSCT plus maintenance therapy (n = 18), 8.4 and 46.8 months, respectively (p = 0.017). Patients treated with chemotherapy alone had also a shorter median overall survival (OS) compared to patients treated with autoHSCT: 13.0 vs. 46.8 months (p = 0.046). The differences remained statistically significant even after excluding patients with Ph positivity. We can conclude that, in our case, autoHSCT followed by maintenance chemotherapy is a good option for adult patients with ALL and, in standard-risk and high-risk patients, provides more favorable OS and PFS rates compared to patients treated by chemotherapy alone. However, we are aware of the fact that our analysis may have been distorted by the fact that the analysis is retrospective, that treatment with autoHSCT was based on patient’s decision, and that chemotherapy may have been administered to negatively selected patients.     

Effect and safety of anlotinib combined with S-1 for recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy

This study aimed to evaluate the effect and safety of anlotinib combined with S-1 in the treatment of recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy.This study retrospectively reviewed 22 recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy between June 1, 2018 and February 28, 2019. All patients did not previously receive anlotinib or S-1.Of 22 patients, 20 patients had squamous cell cancer. Seventeen patients received at least 2 cycles of anlotinib plus S-1. The objective response rate (ORR) was 35.3%, and the disease control rate (DCR) was 82.4%. The median progression-free survival (PFS) was 3.5 months, and median overall survival (OS) was 5.2 months. In the first-line treatment subgroup, the ORR was 50%, the DCR was 80%, the median PFS was 4.5 months, and the median OS was 5.8 months. In the second-line and above treatment subgroup, the ORR was 14.3%, the DCR was 85.7%, the median PFS was 3.0 months, and the median OS was 3.7 months. The main adverse events (AEs) of anlotinib combined with S-1 were fatigue (58.8%), hypertension (47.1%), hemoptysis (29.4%), anemia (29.4%), nausea (23.5%), liver function damage (23.5%), albuminuria (17.6%), abdominal pain (17.6%), leukopenia (17.6%), neutropenia (11.8%), fever (11.8%), and hand-foot syndrome (11.8%). Grade 3 AEs included nausea (5.9%) and hypertension (5.9%), and no grade 4 or more AEs were reported.Anlotinib combined with S-1 achieved promising disease control and satisfactory survival with tolerable safety in recurrent metastatic esophageal cancer who refused or were intolerant to intravenous chemotherapy.     

Efficacy and safety profile of combining agents against epidermal growth factor receptor or vascular endothelium growth factor receptor with gemcitabine-based chemotherapy in patients with advanced pancreatic cancer: A meta-analysis

ObjectivesSeveral clinical trials have been published on gemcitabine-based chemotherapy with or without addition of agents against epidermal growth factor receptor (EGFR) or vascular endothelium growth factor receptor (VEGFR) in patients with advanced pancreatic cancer, however, with diverse results. The objective of this study was to perform a meta-analysis of the published trials.MethodsThe database of CENTRAL, MEDLINE and EMBASE were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated the efficacy and safety profile of adding targeted agents against EGFR or VEGFR to gemcitabine-based chemotherapy in patients with advanced pancreatic cancer. The primary outcome was overall survival (OS) while secondary outcomes included progression free survival (PFS) and overall response rate (ORR). Toxicity profiles were also assessed. Review Manager 5.1 was used to perform the analysis.ResultsResults reported from 6 RCTs involving 2733 patients were included in the analysis. Compared to gemcitabine-based chemotherapy alone, addition of an agent against EGFR resulted in significant longer OS [Hazard ratios (HR) 0.89 (0.79–0.99), p = 0.04] and longer PFS [HR 0.87 (0.79–0.97), p = 0.01], but no significant difference in ORR [RR 1.18 (0.82–1.70), p = 0.36]. The addition of an agent against VEGFR resulted in higher ORR [RR 1.54 (1.03–2.30), p = 0.04], but no advantage in OS [HR 0.95 (0.83–1.09), p = 0.47] or PFS [HR 0.97 (0.77–1.23), p = 0.82].ConclusionsAddition of an agent against EGFR to gemcitabine-based chemotherapy improved OS compared to gemcitabine-based chemotherapy alone in patients with advanced pancreatic cancer, while addition of an agent against VEGFR showed a modest improvement in ORR but not PFS and OS.     

Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin’s lymphoma

The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin’s lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.     

Survival rates for stage II colon cancer patients treated with or without chemotherapy in a population-based setting

Background and aims There is considerable uncertainty as to whether adjuvant 5-fluorouracil-based chemotherapy provides survival benefit for colon cancer patients with stage II disease. Consequently, the current rates of chemotherapy use for this disease are low despite 5-year survival rates of only 70–80%. The aim of the present study is to compare the survival rate of stage II colon cancer patients treated by surgery alone with that of patients also treated by chemotherapy. Patients and methods A population-based observational study was conducted on the survival of stage II colon cancer patients (n = 812) diagnosed in Western Australia from 1993 to 2003. The study was restricted to patients aged ≤75 years, of whom 18% (n = 142) were treated with chemotherapy. Only 0.9% of patients older than 75 years received chemotherapy. Results Patients who received chemotherapy were significantly younger (mean age 6 years) than those treated by surgery alone (65 years, P < 0.001), and their tumors were more often positive for vascular invasion (P = 0.007). Multivariate analysis that included all prognostic factors revealed adjuvant chemotherapy was associated with improved survival (HR = 0.62, 95% CI [0.39–0.98], P = 0.043), with women gaining more benefit (HR = 0.48, 95% CI [0.20–1.22], P = 0.09) than men (HR = 0.94, 95% CI [0.54–1.64], P = 0.8). Conclusions In view of the apparent survival benefit from chemotherapy for stage II colon cancer, the present study raises concerns about the current low rates of adjuvant treatment for this disease in the community, particularly for female patients. Melinda Morris was supported by a Surgeon–Scientist scholarship from the Royal Australasian College of Surgeons.     

Impact of sarcopenia on prediction of progression-free survival and overall survival of patients with pancreatic ductal adenocarcinoma receiving first-line gemcitabine and nab-paclitaxel chemotherapy

Background and aimsSarcopenia is an important prognostic factor for cancer patients. Here, we assessed the effects of sarcopenia on progression-free survival (PFS) and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent treatment with first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX).MethodsThe study enrolled patients with unresectable PDAC who underwent chemotherapy between April 2016 and May 2020. The skeletal muscle index (SMI) at the third lumbar spine level (L3) was calculated from computed tomography (CT) images. Propensity score analysis was used to compare PFS and OS in the sarcopenia and non-sarcopenia groups. Univariate and multivariate analyses were performed to determine variables significantly associated with prognosis.ResultsOf the 176 patients who received first-line GEM and nab-PTX, 84 were selected and divided into two groups of 42 (the sarcopenia and the non-sarcopenia groups) by propensity score matching. The median PFS of the sarcopenia and the non-sarcopenia groups was 5.0 and 8.0 months, respectively (p = 0.004). The median OS was 10.3 and 18.1 months, respectively (p = 0.001). Multivariate analyses revealed that sarcopenia was an independent prognostic factor for PFS and OS (p = 0.004, p = 0.001, respectively). The rates of major grade 3 or 4 AEs were significantly higher in the sarcopenia group (p = 0.008).ConclusionsSarcopenia is an independent indicator of a poor prognosis in patients with PDAC treated with first-line GEM and nab-PTX.     

Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Chinese patients

The objective of this study is to evaluate the long-term efficacy and safety of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in Chinese patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The study comprised a retrospective analysis of patients treated at a single center. Patients received four to six infusions of rituximab (375 mg/m² per dose) on day 1 of each cycle of CHOP chemotherapy. CHOP was initiated on day 3 of each cycle; cycles were repeated at 21-day intervals. A total of 82 patients with a median age of 45 years (range 18–76 years) was included. The overall response (OR) and complete response (CR) rates were 90.2 and 70.7%, respectively. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.4 ± 8.3% and 74.1 ± 7.4%, respectively. Patients with International Prognostic Index (IPI) scores ≤2 had significantly higher OR, CR, PFS, and OS rates (p = 0.01, p = 0.02, p = 0.01, p < 0.001, respectively) compared with patients with IPI scores >2. The hematologic toxicity was mild. Five patients with a history of chronic hepatitis B experienced a reactivation of viral hepatitis. The rituximab–CHOP combination was effective and well tolerated in Chinese patients with newly diagnosed DLBCL. This study was conducted in accordance with the Chinese Good Clinical Practice (GCP), including ethical approval.     

High-dose chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: complete response at transplant predicts survival

Although the role of high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established in several large prospective studies, its effectiveness in patients with peripheral T cell lymphoma (PTCL) has not been defined. We aimed to evaluate the efficacy of HDT and ASCT and prognostic factors for survival in patients with PTCL. We retrospectively analyzed the results of 40 PTCL patients treated with HDT and ASCT at Asan Medical Center between January 1995 and December 2005. Twenty patients had PTCL-U (peripheral T cell lymphoma, unspecified), 10 had extranodal natural killer/T cell lymphoma, 5 had anaplastic large cell lymphoma, 3 had angioimmunoblastic T cell lymphoma, 1 had hepatosplenic γσ T cell lymphoma, and 1 had disseminated mycosis fungoides. Disease status at transplant was complete response (CR)1 in 3 patients, CR2 or greater in 8, partial remission in 25, and refractory in 4. At a median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 46.1%. The median event free survival (EFS) was 3.6 months (95% confidence interval, 2.5 to 4.8 months). Ten patients (25%) remain alive without evidence of disease. The median OS of 11 patients with CR at ASCT was not reached; of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR at ASCT was a prognostic factor for EFS (P = 0.025) and OS (P = 0.027) and normal lactate dehydrogenase (LDH) at ASCT was a prognostic factor for improved OS (P = 0.025). Chemosensitive patients with PTCL who achieved CR before ASCT seem to benefit from HDT and ASCT. Pretransplant values of LDH had potential to predict the survival.     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.     

Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non‐Hodgkin lymphoma: a multicentre phase II study

There is a lack of published data examining non‐cytotoxic options for the frontline treatment of patients with high‐tumour burden (HTB) indolent non‐Hodgkin lymphoma (iNHL). We completed a multicentre phase II study for patients with untreated HTB iNHL (NCT00369707) consisting of three induction cycles of weekly bortezomib and rituximab followed by an abbreviated consolidation. Forty‐two patients were treated and all were evaluable; the most common histology was follicular lymphoma (FL) (n = 33, 79%). Patient characteristics included median age 62 years (40–86); 38% bulky disease; 19% malignant effusions; 91% advanced‐stage disease; and median FL International Prognostic Index (FLIPI) score was 3. Therapy was well tolerated with few grade 3/4 toxicities including minimal neurotoxicity. On intent‐to‐treat, the overall response rate (ORR) at end of therapy was 70% with a complete remission (CR) rate of 40% (FL: ORR 76%, CR 44%). With 50‐month median follow‐up, 4‐year progression‐free survival (PFS) was 44% with 4‐year overall survival (OS) of 87% (FL: 44% and 97%, respectively). Four‐year PFS for FLIPI 0–2 vs. 3–5 was 60% vs. 26% respectively (P = 0·02), with corresponding OS rates of 92% and 81% respectively (P = 0·16). Collectively, bortezomib/rituximab is a non‐cytotoxic therapeutic regimen that was well tolerated and resulted in long‐term survival rates approximating prior rituximab/cytotoxic chemotherapy series for untreated HTB FL.