External beam radiation therapy for locally advanced and metastatic gastrointestinal stromal tumors

BACKGROUND: The role of radiation therapy (RT) in the management of gastrointestinal stromal tumors (GIST) is not well described. Here we report our institutional experience for patients with locally advanced or metastatic GIST treated with RT. METHODS: Between 1997 and 2012, 15 patients with 22 GISTs were treated with RT at our center. The median age was 68 (range, 41–86). Fourteen patients had stage IV disease and 1 patient had stage IIIB disease, per the American Joint Committee on Cancer (AJCC), 7th Edition staging. Tumors were in a variety of locations, and were most commonly referred for palliative treatment. Eighteen of 22 tumors were symptomatic. Prior to RT, 14 of 15 patients received systemic therapy in the form of tyrosine kinase inhibitors (TKIs) (n = 11), chemotherapy (n = 4), or both (n = 1). TKIs were used concurrently for nine tumors (40.9%). No tumors were treated with concurrent chemotherapy. Several fractionation schemes were used, most commonly 3 Gy × 10 (n = 8). Local progression-free survival and overall survival were estimated using the Kaplan-Meier method. Acute toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: The median follow-up was 5.1 months (range, 1.3-28.3). At the time of analysis, 12 patients have died (80%). The estimated 6-month local progression-free survival and overall survival were 57.0% and 57.8%, respectively. Among the 18 symptomatic tumors, at least partial palliation was achieved in 17 (94.4%), and symptoms were completely palliated in eight (44.4%). Treatment was well tolerated, with no Grade 4 or 5 toxicities. There was no Grade ≥3 toxicity associated with concurrent TKI use. CONCLUSIONS: In this largest series to date of GISTs treated with RT, a high rate of palliation was achieved for symptomatic tumors in a cohort of advanced stage, heavily pretreated patients. Treatment was well tolerated, and concurrent use of tyrosine kinase inhibitor therapy was not associated with additional toxicity. While follow-up was short, durable control is possible for some patients, providing evidence that GIST is not universally radioresistant and that RT can provide an important benefit in patients with progressive or metastatic disease

Prevalence of patientreported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

Purpose Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Materials and methods Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45–56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS C 3 and CTCAE C 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen’s kappa coefficient. Results Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of C3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score C3) improved during treatment (13.4% at week 5). ‘‘Poor’’ agreement was observed between patient- and clinician-reported proctitis (Cohen’s k = 0.11; n = 58); however, there was ‘‘good’’ agreement for diarrhea (Cohen’s k = 0.68; n = 58). Conclusions Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4–5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments

Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29

<p>Abstract</p> <p>Purpose</p> <p>To assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort.</p> <p>Methods</p> <p>Patients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients.</p> <p>Results</p> <p>A total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module.</p> <p>Conclusions</p> <p>Our study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.</p

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally-advanced, unresectable non-small cell lung cancer (NSCLC)

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT

FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma

ABSTRACT Background. Reports show that FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) results in objective response rates two to threefold higher than those of other regimens. This study aimed to assess response and resection rates for locally unresectable (stage 3) patients initially treated with induction FOLFIRINOX. Methods. The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010 and 2013. Patients were included in the study if they were treated at the authors&apos; institution for stage 3 PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. Results. The study identified 101 patients. The median age was 64 years (range 37-81 years), and the median followup period was 12 months (range 3-37 months). The patients received a median of six cycles (range 1-20 cycles) of induction FOLFIRINOX. No grade 4 or 5 toxicity was recorded. At the initial restaging (median of 3 months after diagnosis), 23 patients (23 %) had developed distant metastases, 15 patients (15 %) had undergone resection, and 63 patients (63 %) had proceeded to chemoradiation. In the group of 63 patients who had proceeded to chemoradiation (median of 9 months after diagnosis), an additional 16 patients (16 %) had undergone resection, and 5 patients (5 %) had developed metastases. A partial radiographic response was observed in 29 % of all the patients, which was associated with ability to perform resection (p = 0.004). The median overall survival time was 11 months for the group that progressed with FOLFIRINOX and 26 months for the group that did not progress. Conclusion. Nearly one third of the patients who had been initially identified as having stage 3 pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection. A recently completed phase 3 randomized trial for stage 4 pancreatic ductal adenocarcinoma (PDAC) identified FOL-FIRINOX as superior to gemcitabine in terms of radiographic response together with improved progression-free and overall survival. 1 Patients who received FOLFIRINOX experienced a 32 % objective response rate (ORR) compared with 9 % in the gemcitabine arm of the study, which correlated with survival benefit (median overall and progression-free survival, 11 and 6 versus 7 and 3 months, respectively). Retrospective studies of patients with both borderline resectable PDAC (stages 1 and 2) and stage 3 disease (locally unresectable) also have suggested an ORR of approximately 30 % with FOLFIRINOX. 2,3 The reported ORR from non-FOLFIRINOX regimens has generally been in the range of 10 %, including the results of a phase

Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy

Purpose: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. Experimental Design: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. Results: Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), 6 (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors (P = 0.0001). Rectal cancer dMMR tumoroids reflected this resistance to chemotherapy. No genomic predictors of chemotherapy response were identified. Of 16 patients receiving chemoradiation, 13 (93%) experienced tumor downstaging; one patient had stable disease, comparable to 48 pMMR rectal cancers. Of 13 patients undergoing surgery, 12 (92%) had early-stage disease. Forty-two (84%) of the 50 patients tested positive for Lynch syndrome (LS) with enrichment of germline MSH2 and MSH6 mutations when compared to 193 LS-associated colon cancer patients (MSH2, 57% vs 36%; MSH6, 17% vs 9%; P &lt; .003). Conclusions: Over one-fourth of dMMR rectal tumors treated with neoadjuvant chemotherapy exhibited disease progression. Conversely, dMMR rectal tumors were sensitive to chemoradiation. MMR status should be performed upfront in all locally advanced rectal tumors with careful monitoring for response on neoadjuvant chemotherapy and genetic testing for LS in dMMR rectal cancer patients

Erratum to: “Pancreatic cancer and SBRT: A new potential option?” [Rep. Pract. Oncol. Radiother. 20 (2015) 377–384]

Local control remains a major issue for patients with unresectable, locally advanced pancreatic cancer (LAPC). The role of radiation therapy in the management of LAPC represents an area of some controversy. Stereotactic body radiotherapy is an emerging treatment option for LAPC as it can provide a therapeutic benefit with significant advantages for patients’ quality of life over standard conventional chemoradiation. The objective of this review is to present the rationale for stereotactic body radiotherapy in LAPC, as well as to discuss the potential limitations and caveats of the currently available studies

Pancreatic cancer and SBRT: A new potential option?

Local control remains a major issue for patients with unresectable, locally advanced pancreatic cancer (LAPC). The role of radiation therapy in the management of LAPC represents an area of some controversy. Stereotactic body radiotherapy is an emerging treatment option for LAPC as it can provide a therapeutic benefit with significant advantages for patients’ quality of life over standard conventional chemoradiation. The objective of this review is to present the rationale for stereotactic body radiotherapy in LAPC, as well as to discuss the potential limitations and caveats of the currently available studies