Is Extended Volume of External Beam Irradiation Beneficial in Post-esophagectomy High Risk Patients Receiving Combined Chemoradiation Therapy?

OBJECTIVE: To assess the value of extended volume irradiation with anastomotic coverage in high risk resected esophageal cancer patients. METHOD: A retrospective study was undertaken at LRCC from 1989-1999 for high risk resected esophageal cancer patients. Adjuvant treatments consisted of 4 cycles of chemotherapy (epirubicin/fluorouracil/cisplatin or cisplatin/fluorouracil), and local regional irradiation with or without coverage of the anastomotic site. Radiation dose ranged from 45-60Gy at 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage) or small (without anastomotic coverage) field followed by oblique fields for boost. RESULT: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation therapy. Three patients had disease progression prior to therapy, and 69 patients were analyzed. There were 81% T3N1 and 13% T2N1. Thirty-four patients had margin involvements (radial 53%; proximal/distal 32%), 65% were adenocarcinoma and 33% were squamous carcinoma. Median followup was 23.6 months (3.4 - 78.4 months). Two year survival was 50%; 5yr 24%. Relapse rate was 62.3% and median time to relapse was 20 months. Recurrence locally to anastomosis or adjacent to anastomosis was 9/43(20.9%) with small field and 2/26(7.7%) with extended field. Of 31 patients with relapse outside anastomosis, 14/20(70%) relapsed locoregional/distal when treated with small field and 3/11(27%) relapsed locoregional/distal when treated with extended field (p=0.02). There was no excess treatment interruption or chronic gastrointestinal toxicity with extended field irradiation. CONCLUSION: There is significant decrease in locoregional/distal relapse with use of extended field in high risk resected esophageal cancer patients

Extended vs. Small Field Irradiation in High Risk Post Esophagectomy Patients Receiving Combined Chemoradiation Therapy: A Decade Experience in Treatment of Esophageal Cancer

OBJECTIVE: To assess the impact of extended field irradiation with anastomotic coverage on local recurrence in high risk resected esophageal cancerpatients. METHODS: From 1989-1999, high risk resected esophageal cancer cases receiving post-resection chemoradiation were reviewed. Adjuvant chemotherapy consisted of four cycles of fluorouracil-based regimens. Loco-regional irradiation with or without coverage of anastomotic site had radiation a dose range from 45-60 Gyat 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage), or small (without anastomotic coverage) field followed by oblique fields for boost. RESULTS: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation. Three patients had disease progression prior to therapy, and 69 patients were analyzed. The median age was 60 years (range 35-82 years) with 94% T2-3N1 and 65% were adenocarcinoma. As of January 2005 median followup was 30.5 months (range 3-142 months), the two-and five-year overall survival rates were 50% and 31%, respectively. First relapse rate after adjuvant therapy was 71% (n=49) and median time to relapse was about 30 months. Loco-regional relapse with small field was 25/35 (71.4%) and 2/14 (14.2%) with extended field (P\u3c0.001). Recurrence locally to anastomosis or adjacent site was 10/35 (28.6%) with small field and 0/14 (0%) with extended field (P=0.04). CONCLUSION: At a minimum of 5-year followup, there is significant decrease in loco-regional relapse with the use of extended field in high risk resected esophageal cancer patients. This important improvement trend deserves further exploration in prospective randomized clinical trials

First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study

\ua9 2024 The Authors; Published by the American Association for Cancer Research. PURPOSE: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II). RESULTS: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC. CONCLUSIONS: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers. SIGNIFICANCE: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small

Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience

From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m–2), cisplatin (50 mg m–2) administered intravenously on day 1, vincristine (0.6 mg m–2) on day 2 and cyclophosphamide (700 mg m–2) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. © 1999 Cancer Research Campaig

Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor

BACKGROUND: Tumoural interstitial hypertension, possibly modulated by platelet-derived and vascular endothelial growth factor receptors (PDGFR and VEGFR), may mediate resistance to chemotherapy. METHODS: Forty-eight patients with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg twice daily (BID)) and docetaxel (75-100 mg m⁻²), or CP-868,596 (60 mg BID), docetaxel (75 mg m⁻²), and VEGFR inhibitor axitinib (5 mg BID). RESULTS: The CP-868,596/docetaxel was escalated as above. The CP-868,596/docetaxel/axitinib was not dose escalated because of increased incidence of mucositis-like adverse events (AEs) with concurrent neutropenia relative to that expected for docetaxel. All tested regimens were tolerable, including 100 mg BID CP-868,596 (recommended phase II dose) plus 100 mg m⁻² docetaxel (maximum approved dose). Most treatment-emergent AEs were mild-moderate and reversible, commonly including nausea, diarrhoea, vomiting, constipation, fatigue, and anaemia (CP-868,596/docetaxel), and hypertension, lethargy, diarrhoea, and fatigue (CP-868,596/docetaxel/axitnib). Pharmacokinetics were unaffected by co-administration. Twenty-one patients achieved stable disease, including all seven evaluable on CP-868,596/docetaxel/axitinib. All nine CP-868,596/docetaxel/axitinib patients received therapy for a median of six (range, 3-16) cycles. CONCLUSIONS: The CP-868,596/docetaxel was well tolerated, but increased efficacy was not observed. Addition of axitinib delivered greater benefits than expected in the number of patients achieving prolonged stable disease with a moderate increase in AEs

Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

<p>Abstract</p> <p>Background</p> <p>Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated.</p> <p>Methods</p> <p>MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy.</p> <p>Results</p> <p>MSI was found in 43 (13.8%) tumors. Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2–0.7; P = 0.0007) and death (HR = 0.4; 95% CI: 0.2–0.9; P = 0.02) independently of the TS and DPD expressions. A direct relationship between MSI and TS intensity (P = 0.001) was found, while there was no significant association with DPD intensity (P = 0.1).</p> <p>Conclusion</p> <p>The favourable outcome of MSI colorectal carcinomas is ascribed mainly to the tumor biology and to a lesser extent to antitumor response to 5-fluorouracil therapy. There is no evidence that differential TS or DPD expression may account for these outcome characteristics.</p

Predictors of Long-Term Care Utilization by Dutch Hospital Patients aged 65+

Background Long-term care is often associated with high health care expenditures. In the Netherlands, an ageing population will likely increase the demand for long-term care within the near future. The development of risk profiles will not only be useful for projecting future demand, but also for providing clues that may prevent or delay long-term care utilization. Here, we report our identification of predictors of long-term care utilization in a cohort of hospital patients aged 65+ following their discharge from hospital discharge and who, prior to hospital admission, were living at home. Methods The data were obtained from three national databases in the Netherlands: the national hospital discharge register, the long-term care expenses register and the population register. Multinomial logistic regression was applied to determine which variables were the best predictors of long-term care utilization. The model included demographic characteristics and several medical diagnoses. The outcome variables were discharge to home with no formal care (reference category), discharge to home with home care, admission to a nursing home and admission to a home for the elderly. Results The study cohort consisted of 262,439 hospitalized patients. A higher age, longer stay in the hospital and absence of

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig