Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

Successful treatment of recurrent small bowel adenocarcinoma by cytoreductive surgery and chemotherapy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Small bowel adenocarcinoma is a rare malignancy associated with a poor prognosis and there is little evidence of effective treatment. Recurrent small bowel adenocarcinoma is an intractable disease for which there is little information available regarding its treatment by palliative therapy. We present a case of recurrent small bowel adenocarcinoma successfully treated by cytoreductive surgery and palliative chemotherapy.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Japanese female who developed a peritoneal metastasis from recurrent small bowel adenocarcinoma after curative resection and adjuvant chemotherapy with S-1 and polysaccharide K. She underwent cytoreductive surgery followed by chemotherapy with folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K. Subsequently, no sign of a recurrence was observed 42 months after the second operation.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of the successful treatment of peritoneal metastasis from small bowel adenocarcinoma by cytoreductive surgery and combination chemotherapy (folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K).</p

Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective

Background There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. Case The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. Conclusions Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm

Increasing capacity for the treatment of common musculoskeletal problems: A non-inferiority RCT and economic analysis of corticosteroid injection for shoulder pain comparing a physiotherapist and orthopaedic surgeon

Background Role substitution is a strategy employed to assist health services manage the growing demand for musculoskeletal care. Corticosteroid injection is a common treatment in this population but the efficacy of its prescription and delivery by physiotherapists has not been established against orthopaedic standards. This paper investigates whether corticosteroid injection given by a physiotherapist for shoulder pain is as clinically and cost effective as that from an orthopaedic surgeon. Methods A double blind non-inferiority randomized controlled trial was conducted in an Australian public hospital orthopaedic outpatient service, from January 2013 to June 2014. Adults with a General Practitioner referral to Orthopaedics for shoulder pain received subacromial corticosteroid and local anaesthetic injection prescribed and delivered independently by a physiotherapist or a consultant orthopaedic surgeon. The main outcome measure was total Shoulder Pain and Disability Index (SPADI) score at baseline, six and 12 weeks, applying a non-inferiority margin of 15 points. Secondary outcomes tested for superiority included pain, shoulder movement, perceived improvement, adverse events, satisfaction, quality of life and costs. Results 278 participants were independently assessed by the physiotherapist and the orthopaedic surgeon, with 64 randomised (physiotherapist 33, orthopaedic surgeon 31). There were no significant differences in baseline characteristics between groups. Non-inferiority of injection by the physiotherapist was declared from total SPADI scores at 6 and 12 weeks (upper limit of the 95% one-sided confidence interval 13.34 and 7.17 at 6 and 12 weeks, respectively). There were no statistically significant differences between groups on any outcome measures at 6 or 12 weeks. From the perspective of the health funder, the physiotherapist was less expensive. Conclusions Corticosteroid injection for shoulder pain, provided by a suitably qualified physiotherapist is at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care

A description of physical therapists' knowledge in managing musculoskeletal conditions

BACKGROUND: Physical therapists increasingly provide direct access services to patients with musculoskeletal conditions, and growing evidence supports the cost-effectiveness of this mode of healthcare delivery. However, further evidence is needed to determine if physical therapists have the requisite knowledge necessary to manage musculoskeletal conditions. Therefore, the purpose of this study was to describe physical therapists' knowledge in managing musculoskeletal conditions. METHODS: This study utilized a cross-sectional design in which 174 physical therapist students from randomly selected educational programs and 182 experienced physical therapists completed a standardized examination assessing knowledge in managing musculoskeletal conditions. This same examination has been previously been used to assess knowledge in musculoskeletal medicine among medical students, physician interns and residents, and across a variety of physician specialties. RESULTS: Experienced physical therapists had higher levels of knowledge in managing musculoskeletal conditions than medical students, physician interns and residents, and all physician specialists except for orthopaedists. Physical therapist students enrolled in doctoral degree educational programs achieved significantly higher scores than their peers enrolled in master's degree programs. Furthermore, experienced physical therapists who were board-certified in orthopaedic or sports physical therapy achieved significantly higher scores and passing rates than their non board-certified colleagues. CONCLUSION: The results of this study may have implications for health and public policy decisions regarding the suitability of utilizing physical therapists to provide direct access care for patients with musculoskeletal conditions