The significance of Trk receptors in pancreatic cancer.

This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation altered expression of four neuroendocrine genes and whether this resulted in subsequent changes in radiosensitivity. A specific inhibitor of TrkA, B, and C, AstraZeneca 1332, was investigated in vitro and in vivo in combination with radiation. A tissue microarray was constructed from 77 pancreatic ductal adenocarcinoma patients who had undergone neoadjuvant chemoradiation and the Trk receptor, and neurogenic differentiation 1 expression was assessed and correlated with overall survival. A total of 99 genes were identified that were differentially expressed in the chemoradiation patients with neuroendocrine genes and pathways, in particular the neurogenic differentiation 1 and Trk receptor family, being prominent. Fractionated radiation upregulated the expression of neuroendocrine genes, and AstraZeneca 1332 treatment in vitro enhanced radiosensitivity. No added effect of AstraZeneca 1332 was observed in vivo. Trk receptor expression varied between isoforms but did not correlate significantly with clinical outcome. Radiation treatment upregulated neuroendocrine gene expression but the Trk receptor family does not appear to be a promising treatment target.

Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal resection in rectal cancer: patient-reported outcomes in National Surgical Adjuvant Breast and Bowel Project randomized trial R-04.

OBJECTIVE: National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS). METHODS: To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, sex, stage, intended surgery, and randomly assigned chemoradiotherapy. RESULTS: Of 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at 1 year. For the EORTC QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P = 0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS patients reported worse gastrointestinal tract symptoms than did the APR patients (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002). CONCLUSIONS: Symptoms and functional problems were detected at 1 year by EORTC QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer.

Radiation Therapy in the Management of Extensive Giant Condyloma Acuminata With Rectal Involvement: A Case Report.

Giant condyloma acuminata (GCA) is a rare, locally aggressive manifestation of human papillomavirus (HPV) infection, typically affecting the anorectal area. Patients with GCA often have a poor prognosis due to the high risk of malignant transformation. In this case report, we present a 39-year-old man with HIV who developed progressive and refractory anorectal GCA. Despite initially non-cancerous pathology results, there were concerns regarding a malignant component to the mass. Multidisciplinary discussions led to the decision to pursue definitive radiation therapy. This case report and review of the literature highlight the role of radiation in the management of GCA and the importance of a multidisciplinary approach in the treatment of complex cases.

Genomic Classifier Performance in Intermediate-Risk Prostate Cancer: Results From NRG Oncology/RTOG 0126 Randomized Phase 3 Trial.

PURPOSE: Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk stratification in these patients. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up. METHODS AND MATERIALS: After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical failure, local failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors. RESULTS: Two-hundred fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range, 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio [sHR], 1.12; 95% confidence interval [CI], 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 16% for GC high-risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared with 21% for higher GC patients (P-interaction = .04). CONCLUSIONS: This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.

A Personalized Patient Teaching Session at the Time of Radiation Simulation May Improve Patient Satisfaction Scores.

PURPOSE: Radiation therapy simulation is an excellent time for patient education. We implemented a comprehensive personalized patient experience-focused (PX) teaching session at the time of simulation and assessed its effect using patient satisfaction scores. METHODS AND MATERIALS: From February 2016 to June 2018, a single PX-trained radiation therapy therapist met patients at simulation to address and resolve all treatment-related questions. Results from a Centers for Medicare & Medicaid Services approved voluntary patient satisfaction tool were used to assess the effect of this intervention, using tools the patients received during the on-treatment period. Scores from patients contacted by the PX therapist were compared with those of noncontacted patients. RESULTS: For the survey, 1369 patients were contacted (median contact duration, 23 minutes; range, 0-117). Of 732 surveys submitted during this time, 98 were from on-treatment patients (69 contacted, 29 not contacted). The majority of contacted patients and survey responders were women (64% and 62%, respectively), patients with breast cancer (38%, 41%), and patients who had received curative therapy (82%, 69%). Scores from contacted patients were significantly higher for 10 of the 17 questions (registration helpfulness, P = .03; registration wait time, P = .048; facility way finding, P = .03; facility cleanliness, P = .01; treatment staff skill, P = .03; treatment staff concern for questions, P = .003; response to concerns, P = .01; staff worked together, P = .01; overall rating of care, P = .01; and likelihood of recommending care, P = .04) and 4 of the 5 domains (registration, P = .04; facility, P = .03; personal issues, P = .02; overall assessment, P = .002). CONCLUSIONS: Contact by a PX therapist was associated with higher patient satisfaction scores, including areas specifically addressed by the PX teaching session (concerns for questions, response to concerns) as well as other areas (cleanliness, registration wait time).

A population-based analysis of chemoradiation versus radiation alone in the definitive treatment of patients with stage I-II squamous cell carcinoma of the anus.

BACKGROUND: The optimal management of patients with stage I-II squamous cell carcinoma (SCC) of the anus is controversial. The current study evaluates the efficacy of combined chemotherapy and radiation therapy (CRT) versus radiation therapy (RT) alone in the treatment of these patients using the Surveillance, Epidemiology, and End Results (SEER) registries. METHODS: SEER 18 Custom Data registries were queried for patients with stage I-II SCC of the anus. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. RESULTS: A total of 4,288 patients with stage I-II disease were identified, of whom 3,982 (93%) underwent CRT and 306 (7%) underwent RT. Median follow-up was 42 months. Approximately 30.8% had T1 disease and 69.2% had T2-T3 disease. The IPTW-adjusted 5-year overall survival (OS) was 76.7%, with no significant differences between the CRT and RT groups (77% vs. 73.5%, P=0.33). On multivariate IPTW-adjusted analysis, the lack of association between CRT use and OS was upheld (HR, 0.84, 95% CI, 0.65-1.08, P=0.2). On subgroup analyses, 5-year OS was 86% with CRT (n=1,216) and 84.2% with RT (n=103) (P=0.74) in stage I (T1N0) patients, while 5-year OS was 72.8% with CRT (n=2,766) and 66.4% with RT (n=203) (P=0.13) in stage II (T2-3N0) patients. CRT was associated with improved median OS in stage II patients (119 months vs. not reached, P=0.04). CONCLUSIONS: The current study suggests that omission of concurrent chemotherapy is not associated with inferior OS in patients with stage I SCC of the anus. However, combined chemoradiation was superior to radiation alone in patients with stage II disease. Prospective evidence is needed to optimize clinical decision-making in this patient population.

Migrated sternal wire into the right ventricle: case report in cardiothoracic surgery.

Migrating wires as a result of sternal nonunion present clinical challenges. Cardiac Computed Tomographic Angiography helps locate these wires precisely, enabling detailed surgical planning. Sternal wire migration is an infrequent complication following median sternotomy. It is usually encountered among patients with sternal dehiscence. Understanding the location and spatial relationships of structures to the wire can be challenging. (64 slice) with high spatial and temporal resolution affords the possibility of enhancing presurgical planning.

The dose-volume relationship of small bowel irradiation and acute grade 3 diarrhea during chemoradiotherapy for rectal cancer.

PURPOSE: Previous work has found a highly significant relationship between the irradiated small-bowel volume and development of Grade 3 small-bowel toxicity in patients with rectal cancer. This study tested the previously defined parameters in a much larger group of patients. METHODS AND MATERIALS: A total of 96 consecutive patients receiving pelvic radiation therapy for rectal cancer had treatment planning computed tomographic scans with small-bowel contrast that allowed the small bowel to be outlined with calculation of a small-bowel dose-volume histogram for the initial intended pelvic treatment to 45 Gy. Patients with at least one parameter above the previously determined dose-volume parameters were considered high risk, whereas those with all parameters below these levels were low risk. The grade of diarrhea and presence of liquid stool was determined prospectively. RESULTS: There was a highly significant association with small-bowel dose-volume and Grade 3 diarrhea (p < or = 0.008). The high-risk and low-risk parameters were predictive with Grade 3 diarrhea in 16 of 51 high-risk patients and in 4 of 45 low-risk patients (p = 0.01). Patients who had undergone irradiation preoperatively had a lower incidence of Grade 3 diarrhea than those treated postoperatively (18% vs. 28%; p = 0.31); however, the predictive ability of the high-risk/low-risk parameters was better for preoperatively (p = 0.03) than for postoperatively treated patients (p = 0.15). Revised risk parameters were derived that improved the overall predictive ability (p = 0.004). CONCLUSIONS: The highly significant dose-volume relationship and validity of the high-risk and low-risk parameters were confirmed in a large group of patients. The risk parameters provided better modeling for the preoperative patients than for the postoperative patients.

Nasal and sinus disease in cystic fibrosis.

Paranasal and sinus disease is present in almost every patient with cystic fibrosis. However, symptoms are rarely reported. Some aspects including polyposis and microbial flora change with patient age. Endoscopy and computerised tomography have broadened our understanding of how this disease affects the sinuses, including an increased recognition of polyposis than previously thought and identification of several disease specific entities such as abnormalities of the lateral nasal wall and uncinate process. Few randomised, controlled trials evaluating medical or surgical treatments of CF sinus disease exist. Sinus surgery may provide some benefit, though there are no established selection criteria for appropriate candidates. A link between sinus disease and lower respiratory tract function may contribute to general health and survival following lung transplantation. Complications of sinonasal disease in CF are rare and include mucoceles and periorbital abscesses.

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

BACKGROUND: Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. METHODS: The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. RESULTS: A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). CONCLUSIONS: The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

Neoadjuvant PET and MRI-based intensity modulated radiotherapy leads to less toxicity and improved pathologic response rates in locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques and pre-treatment imaging may impact toxicities and pathologic response (PR). Herein we compare intensity modulated radiotherapy (IMRT) and advanced pre-treatment imaging in the neoadjuvant treatment of LARC and resulting impact on toxicities and pathologic outcomes relative to 3 dimensional conformal radiotherapy (3DCRT). METHODS: LARC patients treated at 4 large academic centers in the US from 2007-2016 were reviewed. Patients received 5-FU-based NeoCRT concurrently with IMRT or 3DCRT. PR was recorded as none, partial, or complete. Common terminology for adverse events version 4 was used to grade toxicities. Toxicity rates were compared using Chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. RESULTS: A total of 128 patients were analyzed: 60.1% male and 39.8% female, median age 57.7 years (range, 31-85 years). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3DCRT (48.1%, 23.1% vs. 31.7%, 23.3%), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT and pretreatment PET and/or MRI imaging was significantly associated with increased odds for complete and partial response (OR =2.95, 95% CI: 1.21-7.25, P=0.018; OR =14.70, 95% CI: 3.69-58.78, P<0.0001). Additionally, IMRT was associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, and diverting ostomy (P<0.05). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3DCRT after adjusting for confounders (OR =0.27, 95% CI: 0.08-0.87). CONCLUSIONS: NeoCRT IMRT with pretreatment PET and/or MRI for LARC leads to reduced acute toxicities and improved PR compared to 3DCRT. Given the challenges associated with prospective validation of these data, IMRT with pretreatment PET and/or MRI should be considered standard treatment for LARC.

Phase II Feasibility Study of a Weight Loss Intervention in Female Breast and Colorectal Cancer Survivors (SWOG S1008).

OBJECTIVE: This study aimed to test the feasibility of a 12-month weight loss intervention using telephone-based counseling plus community-situated physical activity (PA) in female breast cancer (BC) and colorectal cancer (CRC) survivors. METHODS: This multisite cooperative group study enrolled sedentary, female, postmenopausal BC and CRC survivors with BMI ≥ 25 kg/m2 to receive 12-month fitness center memberships and telephone counseling encouraging 150 min/wk of PA and a 500-kcal/ddecrease in energy intake. Feasibility criteria included accrual, adherence, and retention. Target weight loss was ≥ 5%. RESULTS: Among 25 BC survivors, median baseline BMI was 37.2 (range: 27.7-54.6), accrual occurred in 10 months, 60% and 28% met diet and exercise goals, 80% provided 12-month measures, and average weight loss was 7.6% (95% CI: -3.9%, 19.2%). Among 23 CRC survivors, median BMI was 31.8 (range: 26.4-48.7), accrual occurred in 24 months, 61% and 17% met diet and exercise goals, 87% provided measures, and average weight loss was 2.5% (95% CI: -8.2%, 13.3%). CONCLUSIONS: It is feasible to recruit and retain BC survivors in a cooperative group diet and PA weight loss trial. BC survivors achieved clinically meaningful weight loss but did not meet a priori adherence goals. In CRC survivors, recruitment was more difficult, and the intervention was less effective.

Variations in Medicare Reimbursement in Radiation Oncology: An Analysis of the Medicare Provider Utilization and Payment Data Set.

PURPOSE: The purposes of this study were to summarize recently published data on Medicare reimbursement to individual radiation oncologists and to identify the causes of variation in Medicare reimbursement in radiation oncology. METHODS AND MATERIALS: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF), which details nearly all services provided by radiation oncologists in 2012, was used for this study. The data were filtered and analyzed by physician and by billing code. Statistical analysis was performed to identify differences in reimbursements based on sex, rurality, billing of technical services, or location in a certificate of need (CON) state. RESULTS: There were 4135 radiation oncologists who received a total of $1,499,625,803 in payments from Medicare in 2012. Seventy-five percent of radiation oncologists were male. The median reimbursement was $146,453. The code with the highest total reimbursement was 77418 (radiation treatment delivery intensity modulated radiation therapy [IMRT]). The most commonly billed evaluation and management (E/M) code for new visits was 99205 (49%). The most commonly billed E/M code for established visits was 99213 (54%). Forty percent of providers billed none of their new office visits using 99205 (the highest E/M billing code), whereas 34% of providers billed all of their new office visits using 99205. For the 1510 radiation oncologists (37%) who billed technical services, median Medicare reimbursement was $606,008, compared with $93,921 for all other radiation oncologists (P<.001). On multivariate analysis, technical services billing (P<.001), male sex (P<.001), and rural location (P=.007) were predictive of higher Medicare reimbursement. CONCLUSIONS: The billing of technical services, with their high capital and labor overhead requirements, limits any comparison in reimbursement between individual radiation oncologists or between radiation oncologists and other specialists. Male sex and rural practice location are independent predictors of higher total Medicare reimbursements.

Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis.

PURPOSE: To compare toxicity after stereotactic body radiation therapy (SBRT) for "central" tumors-within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum-versus noncentral ("peripheral") lung tumors. METHODS AND MATERIALS: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non-small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/ß=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ(2) and 2-tailed t tests, adverse events with χ(2) test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). RESULTS: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. CONCLUSION: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. METHODS: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. RESULTS: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. CONCLUSIONS: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.

The variability of the clinical target volume for rectal cancer due to internal organ motion during adjuvant treatment.

PURPOSE: This study defined the clinical target volume (CTV) for the adjuvant treatment of rectal cancer and applied this definition to multiple CT scans obtained during the typical 5-week course of treatment to measure the modification to the CTV due to internal organ motion that would be needed to define the planning target volume (PTV). METHODS AND MATERIALS: Ten patients with rectal cancer had weekly treatment planning CT scans during adjuvant radiation therapy. All patients were given oral contrast, placed prone on a rigid foam cradle with a depressed area for small bowel exclusion, and instructed to have a full bladder. The CT scans were registered according to the bones of the pelvis, and the CTV was outlined on each CT slice. Movement of the CTV in all dimensions was measured. The CT scan with the lowest and highest bladder volume for each patient was used to calculate the CTV movement due to bladder filling. RESULTS: The largest difference in the CTV occurred 10 cm caudal to the anus, with a standard deviation of 1 cm. Bladder filling displaced the anterior border of the CTV an average of 7 mm over a cranial to caudal length of 2.5 cm. Other borders of the CTV were based on muscle, bone, or major blood vessels and were stable. CONCLUSION: Modification of the CTV to design a PTV can be unequal, with the largest change at the anterior border of the inferior pelvis.

The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer.

PURPOSE: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. METHODS AND MATERIALS: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. RESULTS: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V15) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. CONCLUSIONS: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy for rectal carcinoma.

Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full-dose gemcitabine.

PURPOSE: To determine the maximal tolerated dose of radiation delivered to the primary tumor bed, in combination with full-dose gemcitabine (1000 mg/m(2) weekly x 3), after resection of pancreatic cancer. METHODS AND MATERIALS: Patients with resected pancreatic carcinoma and poor prognostic features, a positive resection margin, or involved lymph nodes were eligible. Radiotherapy (RT) was directed at the preoperative tumor volume with a conformal technique. Regional lymph node basins were not included. The initial starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in 0.2-Gy increments, keeping the duration of RT to 3 weeks. Gemcitabine was given i.v. for 30-40 min at a dose of 1000 mg/m(2) before RT on Days 1, 8, and 15 of a 28-day cycle. After completion of RT and chemotherapy, an additional cycle of gemcitabine was delivered. RESULTS: Between November 1997 and October 2001, 32 patients were entered: 30 after Whipple resection (positive margins in 2, positive nodes in 22, and both in 6), 1 after distal pancreatectomy, and 1 after incomplete resection of a tumor involving the body (both patients with positive margins and nodes). Treatment was well tolerated. Of the 32 patients, 27 completed all protocol therapy and 29 maintained their pretreatment weight within 5%. Five patients experienced dose-limiting toxicity, four with Grade 3 vomiting requiring hospitalization and one fatal toxicity secondary to pneumonia/sepsis. At the final radiation dose level (42 Gy), 2 patients experienced GI dose-limiting toxicity. At the 39-Gy-dose level, 5 of 6 patients were without dose-limiting toxicity. Isolated local or regional progression was documented in 1 patient. Distant progression was documented in 26 of 32 patients (6 with concurrent local or regional progression). The median survival was 16.5 months (95% confidence interval 12.3-19.9) CONCLUSION: The results of our study indicate that the maximal tolerated radiation dose, administered using conformal techniques targeted to the tumor bed, is 39 Gy. In this high-risk population, data on locoregional control suggest that the reduction in radiation dose and field size minimizes toxicity and does not result in excess failures at these sites.

Hospital discharge to other healthcare facilities: impact on in-hospital mortality.

BACKGROUND: In-hospital mortality is frequently used as an outcomes measure for surgical procedures. Recently, hospitals have developed subacute care facilities to allow earlier discharge. Outcomes of patients discharged (transferred) to these units or to other similar facilities may not be captured in reports of in-hospital mortality. STUDY DESIGN: The California Office of Statewide Health Planning and Development (OSHPD) patient discharge abstract database was examined to determine the rates of discharge to other facilities (transfer) and the number of in-hospital deaths occurring during the index hospitalization and after transfer in patients undergoing cardiac surgery procedures. Data were collected for 1997, 1998, and 1999 for coronary artery bypass grafting (CABG-only, n = 82,897), CABG plus additional procedures (CABG-plus, n = 11,869), and valve repair or replacement (Valve-only, n = 14,872). In-hospital mortality and transfer rates (same-day discharge and readmission to another facility) were determined for all hospitals through the index hospitalization and subsequent transfers. RESULTS: Aggregated 3-year in-hospital mortality rates for the index hospitalization were 2.98% for CABG-only, 9.25% for CABG-plus, and 4.85% in Valve-only groups. Transfer rates were 12.41%, 23.16%, and 13.43%, respectively. The percentages of all in-hospital deaths occurring after transfer from the index hospital were 13.5% (385 of 2,857) in CABG-only, 13.3% (168 of 1,266) in CABG-plus, and 11.0% (89 of 811) in Valve-only patients. When corrected for these additional deaths, the actual in-hospital mortality rate was 3.45% for CABG-only, 10.67% for CABG-plus, and 5.45% for Valve-only procedures. CONCLUSIONS: Transfer to another healthcare facility rather than discharge home is a common practice after cardiac surgery. A substantial percentage of in-hospital deaths occurs after discharge from the primary institution.

Relationship of hospital volume to outcome in cardiac surgery programs in California.

There are more than 120 cardiac surgery programs in California. More than half perform less than 200 coronary artery bypass graft (CABG) procedures per year. This study queried the state of California discharge abstract database to analyze the relationship between annual procedural volume and outcomes of all 119 nonfederal hospitals performing cardiac surgery during 1997 through 1999. Unadjusted in-hospital mortality for CABG surgery was 3.91 per cent (923 of 23,619) in hospitals performing fewer than 200 procedures per year and 2.09 per cent (496 of 23,704) in hospitals performing > or = 500 procedures annually (P = 0.001 by Chi-square). Similar findings were noted for CABG + valve and/or aneurysm and for valve procedures. Risk-adjusted CABG data obtained from 78 of 119 hospitals found that a significant difference persisted between a volume of < 200 and > or = 200 procedures per year (P = 0.03 by t test). There was wider variation in outcome among lower-volume hospitals. However, many low-volume providers had excellent results. It is concluded that although volume is clearly related to outcome patient-related factors and process variables may be more important. Performance improvement programs should be developed to improve communication between providers with differing outcomes.