"HEATPAC" - a phase II randomized study of concurrent thermochemoradiotherapy versus chemoradiotherapy alone in locally advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a dismal prognosis with 5-year overall survival rate of around 5%. Although surgery is still the best option in operable cases, majority of the patients who present in locally advanced stages are deemed inoperable. Novel approaches are therefore needed for the management of around 80% of these inoperable locally advanced pancreatic cancers (LAPC). Hyperthermia (39-43 °C) is a potent radiosensitizer and further enhances the action of gemcitabine, also a known radiosensitizer. Thus through triple sensitization, a combination of hyperthermia, radiotherapy and gemcitabine could be expected to improve the therapeutic outcomes in LAPC. METHODS: This phase II randomized trial, HEATPAC in unresectable LAPC, explores the feasibility and efficacy of concurrent thermochemoradiotherapy (HTCTRT) over chemoradiotherapy (CTRT) alone with pre- and post-intervention FOLFIRINOX at standard dosage and schedule. Following 4 cycles of neoadjuvant FOLFIRINOX, patients with no metastasis and absence of gross peritoneal carcinomatosis would be randomized to either (a) control arm: concurrent CTRT with gemcitabine (400 mg/m2, weekly ×6) or (b) study arm: locoregional hyperthermia (weekly ×6 during radiotherapy) with concurrent CTRT (same as in control arm). All patients would receive simultaneous-integrated boost intensity-modulated radiation therapy to doses of 56Gy and 50.4Gy to the gross and clinical target volumes respectively delivered in 28 fractions over 5.5 weeks. Deep locoregional hyperthermia would be administered weekly and monitored with real-time intraduodenal multisensor thermometry probe. A temperature of 40-43 °C for 60 min would be aimed for each hyperthermia session. On completion of CTRT/HTCTRT, patients of both groups would receive an additional 8 cycles of FOLFIRINOX. DISCUSSION: The expected 1-year baseline overall survival with CTRT alone is considered as 40%. With HTCTRT, a survival advantage of +20% is expected. Considering α = 0.05 and ß = 0.80 for sample size computation, a total of 86 patients would be equally randomized into the two treatment groups. This phase II study if found to be safe and effective, would form the basis of a future phase III randomized study. TRIAL REGISTRATION: The trial has been registered with the ClinicalTrials.gov ( NCT02439593 ). The study has been approved by the Ethical Commissions of Basel and Zurich and is open for patient recruitment.

Radiotherapy infrastructure and human resources in Switzerland : Present status and projected computations for 2020.

PURPOSE: The purpose of this study was to evaluate the present status of radiotherapy infrastructure and human resources in Switzerland and compute projections for 2020. MATERIALS AND METHODS: The European Society of Therapeutic Radiation Oncology "Quantification of Radiation Therapy Infrastructure and Staffing" guidelines (ESTRO-QUARTS) and those of the International Atomic Energy Agency (IAEA) were applied to estimate the requirements for teleradiotherapy (TRT) units, radiation oncologists (RO), medical physicists (MP) and radiotherapy technologists (RTT). The databases used for computation of the present gap and additional requirements are (a) Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) for cancer incidence (b) the Directory of Radiotherapy Centres (DIRAC) of the IAEA for existing TRT units (c) human resources from the recent ESTRO "Health Economics in Radiation Oncology" (HERO) survey and (d) radiotherapy utilization (RTU) rates for each tumour site, published by the Ingham Institute for Applied Medical Research (IIAMR). RESULTS: In 2015, 30,999 of 45,903 cancer patients would have required radiotherapy. By 2020, this will have increased to 34,041 of 50,427 cancer patients. Switzerland presently has an adequate number of TRTs, but a deficit of 57 ROs, 14 MPs and 36 RTTs. By 2020, an additional 7 TRTs, 72 ROs, 22 MPs and 66 RTTs will be required. In addition, a realistic dynamic model for calculation of staff requirements due to anticipated changes in future radiotherapy practices has been proposed. This model could be tailor-made and individualized for any radiotherapy centre. CONCLUSION: A 9.8 % increase in radiotherapy requirements is expected for cancer patients over the next 5 years. The present study should assist the stakeholders and health planners in designing an appropriate strategy for meeting future radiotherapy needs for Switzerland.

Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements?

PURPOSE: To study the potential reduction of dose to organs at risk (OARs) with intensity-modulated proton radiotherapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) photon radiotherapy for left-sided breast cancer patients. METHODS AND MATERIALS: Comparative treatment-planning was performed using planning computed tomography scans of 20 left-sided breast cancer patients. For each patient, three increasingly complex locoregional volumes (planning target volumes [PTVs]) were defined: whole breast (WB) or chest wall (CW) = (PTV1), WB/CW plus medial-supraclavicular (MSC), lateral-supraclavicular (LSC), and level III axillary (AxIII) nodes = (PTV2) and WB/CW+MSC+LSC+AxIII plus internal mammary chain = (PTV3). For each patient, 3D-CRT, IMRT, and IMPT plans were optimized for PTV coverage. Dose to OARs was compared while maintaining target coverage. RESULTS: All the techniques met the required PTV coverage except the 3D-CRT plans for PTV3-scenario. All 3D-CRT plans for PTV3 exceeded left-lung V20. IMPT vs. 3D-CRT: significant dose reductions were observed for all OARs using IMPT for all PTVs. IMPT vs. IMRT: For PTV2 and PTV3, low (V5) left lung and cardiac doses were reduced by a factor >2.5, and cardiac doses (V22.5) were by a factor of >20 lower with IMPT compared with IMRT. CONCLUSIONS: When complex-target irradiation is needed, 3D-CRT often compromises the target coverage and increases the dose to OARs; IMRT can provide better results but will increase the integral dose. The benefit of IMPT is based on improved target coverage and reduction of low doses to OARs, potentially reducing the risk of late-toxicity. These results indicate a potential role of proton-radiotherapy for extended locoregional irradiation in left breast cancer.