No abstract

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour control in silico in several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using 18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10−5) well above levels required to completely ablate a ∼10 cm3 tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.

N Context.-Our cytology laboratory, like many others, is under pressure to improve quality and provide test results faster while decreasing costs. We sought to address these issues by introducing new technology and lean principles.Objective.-To determine the combined impact of the FocalPoint Guided Screener (GS) Imaging System (BD Diagnostics-TriPath, Burlington, North Carolina) and lean manufacturing principles on the turnaround time (TAT) and productivity of the gynecologic cytology operation.Design.-We established a baseline measure of the TAT for Papanicolaou tests. We then compared that to the performance after implementing the FocalPoint GS Imaging System and lean principles. The latter included value-stream mapping, workflow modification, and a first in-first out policy.Results.-The mean (SD) TAT for Papanicolaou tests before and after the implementation of FocalPoint GS Imaging System and lean principles was 4.38 (1.28) days and 3.20 (1.32) days, respectively. This represented a 27% improvement in the average TAT, which was statistically significant (P , .001). In addition, the productivity of staff improved 17%, as evidenced by the increase in slides screened from 8.85/h to 10.38/h. The false-negative fraction decreased from 1.4% to 0.9%, representing a 36% improvement.Conclusions.-In our laboratory, the implementation of FocalPoint GS Imaging System in conjunction with lean principles resulted in a significant decrease in the average TAT for Papanicolaou tests and a substantial increase in the productivity of cytotechnologists while maintaining the diagnostic quality of gynecologic cytology.

5065 Background: SRT is increasingly considered to delay the need to change systemic therapy in metastatic cancer patients who develop oligoprogression. This prospective phase II study evaluated the use of SRT in the setting of mRCC patients who developed oligoprogression while on 1st or 2nd line TKI therapy. Methods: IMDC favourable or intermediate risk mRCC patients (pts) who had previous stability or response on ≥ 3 months of TKI therapy were eligible if they developed radiographic progression of ≤ 5 metastases. The oligoprogressive tumours were treated with SRT while other metastases which were stable or responding to TKI therapy were left alone. TKI therapy was temporarily stopped during SRT, and the same TKI drug then resumed. Endpoints included local control of the irradiated lesions, progression free survival (PFS), overall survival (OS), and cumulative incidence of changing systemic therapy after study entry. Results: 37 pts (median age 63, IMDC favourable 12, intermediate 25) with 57 oligoprogressive tumours were enrolled. 35 pts were on sunitinib and 2 on pazopanib. Median duration of TKI therapy prior to study entry was 18.6 months. 4 pts had IL-2 therapy prior to a 2nd line TKI. 21 pts had a solitary oligoprogressive tumour, while 17 pts had 2-3 oligoprogressive tumours treated with SRT. Median biological effective dose (BED10) was 72 Gy, corresponding to an SRT dose of 40 Gy in 5 fractions. Irradiated tumour sites were the following: 21 lung/pleural, 15 bone, 7 lymph node, 4 adrenal, 4 liver, 3 brain, 2 spleen, and 1 pancreas. At a median followup of 11.6 (1.8-53.5) months the median PFS from study entry was 9.6 months (95%CI 7.4-20.5) with the vast majority of progression occurring outside of the irradiated areas. The 2-year local control of the irradiated tumours was 96%. The 2-year OS from study entry was 77%. The cumulative incidence of changing systemic therapy was 47% at 1 year and 75% at 2 years, with a median time to a change in systemic therapy of 12.6 months. There were no grade 3-5 SRT related toxicities. Conclusions: To our knowledge, this is the first prospective evaluation of the use of SRT for oligoprogressive metastatic cancer. Local control of irradiated oligoprogressive mRCC tumours was high. After delivering SRT, mRCC patients did not need a change in their systemic therapy for a median of 1 year, effectively increasing the PFS of their TKI therapy. This novel approach should be studied in patients with oligoprogression on immunotherapy. Clinical trial information: NCT02019576 .

Background In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp)

e15550 Background: Locally advanced esophageal cancer (LAEC) has a 5-year survival of < 30 %. Most patients (pts) fail after curative intent tri-modality treatment with distant metastatic disease. This phase II trial aims to determine if adjuvant targeted therapy, after neoadjuvant CRT plus surgery for resectable LAEC, may impact on systemic disease without significant toxicity. Methods: Pts with LAEC of the thoracic esophagus or gastroesophageal junction, ECOG PS 0,1 and surgical candidates treated with: preoperative Irinotecan (65mg/m2 initially, ammended to 50mg/m2) + Cisplatin (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (50Gy/25 fractions) on weeks 4–8. Esophagectomy during weeks 15–18. Sunitinib 37.5mg daily (escalating to 50mg daily if tolerated) commenced 4–12 weeks post surgery, for 1 year. Primary endpoint is feasibility and efficacy of adjuvant sunitinib. Planned sample size 36pts. Results: 30pts enrolled from 11/06 to 12/08. Median age 64 yr (43–71), male: 22, adenocarcinoma: squamous 22:6; 10 pts stage IIA, 5 IIB and 13 III. 2 pts excluded with positive PET scan. 28 pts completed CRT - 18 pts (64%) received ≥80% of planned chemotherapy dose, 23 pts (82%) received full radiation dose. Grade 3/4 toxicity included: neutropenia (17/28), diarrhea (7/28), dehydration (4/28), febrile neutropenia (FN) (3/28) and nausea (2/28). 2 deaths on chemotherapy (1 bacterial meningitis, 1 FN) leading to irinotecan dose- reduction. Dysphagia improved in 14/23 pts during CRT. 18 pts have undergone esophagectomy. Complete pathological response in 4 (22%), downstaging in 3 (17%), stable disease in 11 (61%). 2 pts unresectable (metastases at laparotomy). 1 post-operative death due to pulmonary embolus. 9 pts have commenced sunitinib, 6 maintained at starting dose of 37.5mg; 2 dose reductions; 1 discontinued with poor wound healing. Grade 3 toxicity included: leukopenia (2/9), hand-foot reaction (1/9) and depression (1/9). Conclusions: In LAEC, induction Irinotecan/Cisplatin and radiotherapy followed by esophagectomy is associated with a significant but manageable toxicity profile. Early initiation of sunitinib is feasible and well-tolerated. Updated results to be presented. No significant financial relationships to disclose.

No abstract

Purpose To determine the prognostic value of sarcopenia measurements done on staging [18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Methods Patients with early stage, surgically treated esophageal adenocarcinoma and available pre-treatment PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. Results Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, Lymphovascular Invasion (LVI) positive lymph nodes and sarcopenia were significant prognostic factors concerning RFS, and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Conclusion Combining the patients’ imaging derived sarcopenic status with standard clinical data, but not metabolic parameters offered an overall improved prognostic value concerning OS and RFS.