Radiomic Profiling of Head and Neck Cancer: 18F-FDG PET Texture Analysis as Predictor of Patient Survival.

Background and Purpose: The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy. Methods: We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18F-FDG PET/CT before treatment. 18F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c-index was employed to score the predictive power of the multivariate cox regression models. Results: Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P=0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c-index of 0.76 against 0.65 of the model based on clinical variables alone. Conclusion: LILRE, evaluated on pretreatment 18F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control.

Feasibility of voxel-based Dose Painting for recurrent Glioblastoma guided by ADC values of Diffusion-Weighted MR imaging.

PURPOSE: Glioblastoma Multiforme (GBM) is the most common malignant brain tumor and frequently recurs in the same location after radiotherapy. Intensive treatment targeting localized lesion is required to improve GBM outcome, but dose escalation using conventional methods is limited by healthy tissue tolerance. Helical Tomotherapy (HT) Dose Painting (DP) treatments were simulated to safely deliver high doses in the recurrent regions. MATERIALS AND METHODS: Apparent Diffusion Coefficient (ADC) data from five recurrent GBM were retrospectively considered for planning. Hypo-fractionated (25-50Gy, 5 fractions) voxel-based prescriptions were opportunely converted to personalized structured-based dose maps to create DP plans with a commercial Treatment Planning System. Optimized plans were generated and analyzed in terms of plan conformity to dose prescription (Q0.90-1.10), tolerance of the healthy tissues (DMAX), and dosimetry accuracy of the deliverable plans (γ-index). RESULTS: Only three of the five cases could receive a safe retreatment without violating the maximum critical organs dose constraints. The conformity of the simulated plans was between 40.9% and 79.9% (Q0.90-1.10), their delivery time was in the range of 38.3-63.6min, while the dosimetry showed γ-index of 82.4-92.4%. CONCLUSIONS: This study proved the ability of our method to simulate personalized, deliverable and dosimetrically accurate DPBN plans. HT hypo-fractionated treatments guided by ADC maps can be realized and applied to deliver high doses in the GBM recurrent regions, although there are some critical issues related to low Q0.90-1.10 values, to exceeding of healthy-tissue dose constraints for some patients and long delivery times.

Bladder spatial-dose descriptors correlate with acute urinary toxicity after radiation therapy for prostate cancer.

PURPOSE: To assess bladder spatial-dose parameters predicting acute urinary toxicity after radiotherapy for prostate cancer (PCa) through a pixel-wise method for analysis of bladder dose-surface maps (DSMs). MATERIALS & METHODS: The final cohort of a multi-institutional study, consisting of 539 patients with PCa treated with conventionally (CONV:1.8-2Gy/fr) or moderately hypo-fractionated radiotherapy (HYPO:2.2-2.7Gy/fr) was considered. Urinary toxicity was evaluated through the International Prostate Symptoms Score (IPSS) administered before and after radiotherapy. IPSS increases ⩾10 and 15 points at the end of radiotherapy (ΔIPSS⩾10 and ΔIPSS⩾15) were chosen as endpoints. Average DSMs (corrected into 2Gy-equivalent doses) of patients with/without toxicity were compared through a pixel-wise method. This allowed the extraction of selected spatial descriptors discriminating between patients with/without toxicity. Previously logistic models based on dose-surface histograms (DSH) were considered and replaced with DSM descriptors. Discrimination power, calibration and log-likelihood were considered to evaluate the impact of the inclusion of spatial descriptors. RESULTS: Data of 375/539 patients were available. ΔIPSS⩾10 was recorded in 76/375 (20%) patients, while 30/375 (8%) experienced ΔIPSS⩾15. The posterior dose at 12mm from the bladder base (roughly corresponding to the trigone region) resulted significantly associated to toxicity in the whole/HYPO populations. The cranial extension of the 75Gy isodose along the bladder central axis was the best DSM-based predictor in CONV patients. Multi-variable models including DSM descriptors showed better discrimination (AUC=0.66-0.77) when compared to DSH-based models (AUC=0.58-0.71) and higher log-likelihoods. CONCLUSION: DSMs are correlated with the risk of acute GU toxicity. The incorporation of spatial descriptors improves discrimination and log-likelihood of multi-variable models including dosimetric and clinical parameters.

Bladder dose-surface maps and urinary toxicity: Robustness with respect to motion in assessing local dose effects.

The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM). Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70-72.8Gy at 2.5-2.6Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose-volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs. In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4cm(2)) and volumes (<8.4cm(3)) at the highest doses. The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1Gy, with population systematic and random errors within 4 and 3Gy, respectively. The region surrounding this area shows higher mean systematic errors (1-3Gy), population systematic (8-11Gy) and random (5-7Gy) errors. In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5-3.5cm from the base. Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling.

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Efficacy and feasibility of induction chemotherapy and radiotherapy plus cetuximab in head and neck cancer.

BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

PET/CT and radiotherapy : data transfer, radiotherapy workflow and quality assurance.

The development of new technologies in radiation therapy has made it possible to introduce more sophisticated techniques that can deliver the prescribed dose with more conformation and accuracy and to apply dose escalation protocols without increasing the risk of healthy tissue damage. This has consented the simultaneous delivery of different dose levels to different parts of the target, making it possible to boost those tumour sub-volumes that are considered more radio resistant. The use of PET for radiotherapy planning purposes has become increasingly important in the last few years, because of its ability to provide valuable biologic and functional data. PET imaging can affect the treatment strategy definition and improve the target delineation and the assessment of therapy response. The most attractive aspect is the perspective to deliver differential doses inside target volumes for areas of different biologic behaviour based on functional imaging, moving closer to the goals of biologically conformal radiation therapy. Each single step of PET/CT-guided radiotherapy workflow, needs to be performed following high standard procedures, within a rigorous and appropriate quality assurance protocol to minimize the sources of errors and to maximize the efficacy of PET imaging in radiation therapy, ensuring safe and effective use of the technology. The present paper focuses on aspects concerning the use of PET/CT in radiation treatment process, with the aim to delineate different possible approaches to its clinical application and to highlight the critical aspects of the various subprocesses.

Neoadjuvant chemotherapy with continuous infusion of cisplatin and fluorouracil in stage II-IV, M0 squamous cell carcinoma of the head and neck.

AIMS AND BACKGROUND: The aim of the study was to assess the activity and the toxicity of cisplatin (DDP) and fluorouracil (FU) administered by continuous infusion as neoadjuvant chemotherapy for patients with stage II-IV, M0 squamous cell carcinoma of the head and neck. METHODS: Thirty previously untreated patients were submitted to chemotherapy with DDP (20 mg/m2) and FU (1000 mg/m2), both in continuous infusion for 5 days, repeated every 21 days, for a maximum of 5 cycles. Following completion of chemotherapy, the patients underwent radiotherapy; in some patients surgery was performed immediately after chemotherapy. All patients were monitored for response, time to failure, survival, treatment-related events and toxicity. RESULTS: All patients were evaluated for response; after chemotherapy the complete response rate was 27% and the partial response rate 33%. Twenty-four patients underwent radiotherapy: the overall response rate was 83% (complete response 79%). After a median follow-up of 34 months, the median survival time was 22 months with a median time to failure of 15 months. Acute vascular accidents were the main and unexpected adverse events, with 2 deaths for pulmonary embolism and 1 for stroke. The response rate to the regimen does not seem to be better than that obtained with the standard combination of cisplatin bolus and fluorouracil continuous infusion. The disadvantage of the regimen is that it causes more discomfort for the patient in that it requires hospitalization. CONCLUSIONS: For this reason, we believe that there are no elements for recommending the schedule as neoadjuvant treatment of patients with squamous cell carcinoma of the head and neck or as an experimental arm in a randomized trial.

Postradiation sarcoma of head and neck: report of two cases.

AIMS AND BACKGROUND: Post-irradiation sarcoma (PIS) a rare, late side effect of radiotherapy and, consequently, its natural history is not well known. For this reason, two cases treated between 1975 and 1990 are described. CASE REPORTS: The Authors describe one case of malignant fibrous histiocytoma grown in the larynx 111 months after conservative surgery and postoperative radiotherapy, and one case of soft tissue sarcoma developed in the oral cavity 72 months after radical interstitial low dose rate brachytherapy. Both patients had chronic distress of the soft tissues after the primary treatment. The patients are alive and well respectively at 94 and 18 months from salvage surgery. DISCUSSION: The PIS of the head and neck region is a rare event, usually with a bad prognosis. An improvement in results could be possible with early diagnosis, followed by a timely excision, when anatomically possible. As the chronic suffering of the irradiated tissues may increase the risk of PIS, a longer and more frequent follow-up is advisable in these cases.

[Adjuvant radiotherapy in rectal neoplasms. Survival analysis,local control, prognostic factors and toxicity]. / Radioterapia adiuvante nelle neoplasie del retto. Analisi di sopravvivenza, controllo locale, fattori prognostici e tossicità.

January 1985 to June 1991, seventy-five patients affected with surgically treated rectal cancer received adjuvant postoperative irradiation at the Radiation Therapy Department of the Ospedale S. Maria Nuova, Reggio Emilia, Italy. Forty-seven patients had Astler-Coller B2-B3 lesions and 28 had stage C2-C3 disease. The patients underwent postoperative irradiation (range: 44-60 Gy, median: 48.5 Gy) with a 60 Co unit, most of them with conventional fractionation; no patient received adjuvant chemotherapy. A local boost was used in 19 cases (5.4-14 Gy); actuarial 5-year overall and disease-free survival rates were 55.2 +/- 10.5% and 53.4 +/- 10%, respectively; actuarial 5-year local control was 78.7 +/- 10.5%. In 11 cases (14.5%) chronic sequelae were observed; 6 cases required surgical intervention. In 42% of cases the disease relapsed, locally in 12 patients (16%). In conclusion, our results are in agreement with literature data; adequate and innovative techniques are required to decrease treatment-related toxicity.