Brachytherapy or external beam radiotherapy as a boost in locally advanced cervical cancer: a Gynaecology Study Group in the Italian Association of Radiation and Clinical Oncology (AIRO) review.

This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.

Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Radiomics classifier to quantify automatic segmentation quality of cardiac sub-structures for radiotherapy treatment planning.

PURPOSE: A radiomics features classifier was implemented to evaluate segmentation quality of heart structures. A robust feature set sensitive to incorrect contouring would provide an ideal quantitative index to drive autocontouring optimization. METHODS: Twenty-five cardiac sub-structures were contoured as regions of interest in 36 CTs. Radiomic features were extracted from manually-contoured (MC) and Hierarchical-Clustering automatic-contouring (AC) structures. A robust feature-set was identified from correctly contoured CT datasets. Features variation was analyzed over a MC/AC dataset. A supervised-learning approach was used to train an Artificial-Intelligence (AI) classifier; incorrect contouring cases were generated from the gold-standard MC datasets with translations, expansions and contractions. ROC curves and confusion matrices were used to evaluate the AI-classifier performance. RESULTS: Twenty radiomics features, were found to be robust across structures, showing a good/excellent intra-class correlation coefficient (ICC) index comparing MC/AC. A significant correlation was obtained with quantitative indexes (Dice-Index, Hausdorff-distance). The trained AI-classifier detected correct contours (CC) and not correct contours (NCC) with an accuracy of 82.6% and AUC of 0.91. True positive rate (TPR) was 85.1% and 81.3% for CC and NCC. Detection of NCC at this point of the development still depended strongly on degree of contouring imperfection. CONCLUSIONS: A set of radiomics features, robust on "gold-standard" contour and sensitive to incorrect contouring was identified and implemented in an AI-workflow to quantify segmentation accuracy. This workflow permits an automatic assessment of segmentation quality and may accelerate expansion of an existing autocontouring atlas database as well as improve dosimetric analyses of large treatment plan databases.

Rapid and sustained response of an intra- and extracranial large cell lymphoma mass to liposomal intrathecal Ara-C and R-MegaCEOP systemic chemotherapy.

Prognosis of patients suffering from secondary central nervous system (CNS) lymphoma is dismal. Intracranial spread of a lymphoma arising in adjacent extranodal tissues is a rare event. A 32-year-old patient was diagnosed with progressive diffuse large B-cell lymphoma (DLBCL) with extra- and intracranial localization. He complained of headache, left diplopia, marked rigidity of the neck muscles, and difficulty in swallowing and articulating words, caused by bilateral palsy of the XII cranial nerve. Computed tomography (CT) and positron emission tomography (PET) scans showed disease localizations in the occipital-cervical soft tissue, and cerebellar parenchyma. Due to the severity of the clinical picture, high-dose dexamethasone was immediately administered. Mild improvement was observed during the first 2 days of treatment, but dramatic reduction of symptoms and nerve palsy was documented only in the 48 h after the first intrathecal administration of liposomal Ara-C. Systemic R-MegaCEOP chemotherapy was started 7 days later. Concomitant intrathecal liposomal Ara-C injections were continued for a total of nine administrations during the eight cycles of immunochemotherapy without any toxicity observed. Interim and post-therapy PET showed complete resolution of radionuclide accumulation in the involved sites. Consolidation radiotherapy (36 Gy) was administered in involved areas after the completion of the immunochemotherapy program. At the time of writing, no cumulative neurotoxicity is evident at follow-up of 17 months from diagnosis and 9 months after the overall therapeutic program has been accomplished.

Hierarchical clustering applied to automatic atlas based segmentation of 25 cardiac sub-structures.

PURPOSE: Segmentation of cardiac sub-structures for dosimetric analyses is usually performed manually in time-consuming procedure. Automatic segmentation may facilitate large-scale retrospective analysis and adaptive radiotherapy. Various approaches, among them Hierarchical Clustering, were applied to improve performance of atlas-based segmentation (ABS). METHODS: Training dataset of ABS consisted of 36 manually contoured CT-scans. Twenty-five cardiac sub-structures were contoured as regions of interest (ROIs). Five auto-segmentation methods were compared: simultaneous automatic contouring of all 25 ROIs (Method-1); automatic contouring of all 25 ROIs using lungs as anatomical barriers (Method-2); automatic contouring of a single ROI for each contouring cycle (Method-3); hierarchical cluster-based automatic contouring (Method-4); simultaneous truth and performance level estimation (STAPLE). Results were evaluated on 10 patients. Dice similarity coefficient (DSC), average Hausdorff distance (AHD), volume comparison and physician score were used as validation metrics. RESULTS: Atlas performance improved increasing number of atlases. Among the five ABS methods, Hierarchical Clustering workflow showed a significant improvement maintaining a clinically acceptable time for contouring. Physician scoring was acceptable for 70% of the ROI automatically contoured. Inter-observer evaluation showed that contours obtained by Hierarchical Clustering method are statistically comparable with them obtained by a second, independent, expert contourer considering DSC. Considering AHD, distance from the gold standard is lower for ROIs segmented by ABS. CONCLUSIONS: Hierarchical clustering resulted in best ABS results for the primarily investigated platforms and compared favorably to a second benchmark system. Auto-contouring of smaller structures, being in range of variation between manual contourers, may be ideal for large-scale retrospective dosimetric analysis.

Magnetic Resonance Imaging Derived Biomarkers of IDH Mutation Status and Overall Survival in Grade III Astrocytomas.

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher's exact test, Student's t-test, Spearman's Test and receiver operating characteristic analysis. A p ≤ 0.05 value was considered statistically significant for all the tests. A younger age and a frontal location were more likely related to mutational status. IDH-wild type (Wt) exhibited a slight enhancement (p = 0.039). The ADCm values in IDH-mutant (Mut) patients were higher than those of IDH-Wt patients (p < 0.0004). The value of ADC ≥ 0.99 × 10-3 mm2/s emerged as a "cut-off" to differentiate the mutation state. In the overall group, a positive relationship between the ADCm values and OS was detected (p = 0.003; r = 0.62). Adding quantitative measures of ADC values to conventional MR imaging could be used routinely as a noninvasive marker of specific molecular patterns.

Role of perfusion CT in the evaluation of functional primary tumour response after radiochemotherapy in head and neck cancer: preliminary findings.

OBJECTIVE: To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (∆PCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response. METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ∆PCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria. RESULTS: Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p < 0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14 s; p = 0.722). Differently, a significant reduction of all PCTp (p < 0.001) including MTT (from 6.18 to 2.24 s; p = 0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p = 0.037) with the trend also at 3 weeks (p = 0.099) at the multivariate analysis. CONCLUSION: Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response. ADVANCES IN KNOWLEDGE: This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT.

Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is one of the most common malignancies and main causes of cancer death in Western countries. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical 'entity' of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. In this patient group, the use of stereotactic body radiotherapy (SBRT) or other local therapies against all active sites of disease revealed by 18F-choline positron emission tomography/computed tomography (PET/CT) could achieve sufficient prostate-specific antigen (PSA) control. However, a clear benefit of this procedure in terms of significant endpoints is yet to be demonstrated. This case report describes our experience with treating a castration-resistant PCa patient with 18F-choline PET/CT-guided SBRT. Because of the occurrence of 5 metachronous lesions over 4 years, the pattern of recurrence was defined by the local multidisciplinary team as oligometastatic disease, and the patient was treated with 5 courses of SBRT which yielded good PSA control. He started systemic therapy with abiraterone acetate almost 5 years after the diagnosis of recurrent PCa.

[(18)F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results.

BACKGROUND: A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [(18)F]Choline ([(18)F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). METHODS: Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [(18)F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [(18)F]FMCHPET/CT. RESULTS: A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. CONCLUSIONS: Repeated salvage [(18)F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.

Akt1 rs2498801 is related to survival in head and neck squamous cell cancer treated with radiotherapy.

BACKGROUND: Radiotherapy (RT) with or without chemotherapy (CT) plays an important role as exclusive treatment in patients with head and neck squamous cell cancer (HNSCC). Unfortunately, in some cases, benefit for patients is not recorded and only treatment-related complications are registered. MATERIALS AND METHODS: Data relating to Akt1 single nucleotide polymorphism (SNP) and response to treatment of 46 patients treated with exclusive RT or RT-CT for HNSCC were evaluated. RESULTS: For heterozygous patients median overall survival was 28.5 months, while for the wild-type group median overall survival was 10.9 (p=0.019). Three-year survival was 85% for mutated Akt1 homozygosis and 40% for patients with a heterozygous status (p=0.019, hazard ratio (HR)=7.960). CONCLUSION: SNP of rs2498804 can recognize patients resistant to RT-CT. Further studies are needed to confirm our data and to investigate the role of Akt SNPs in HNSCC patients.

Radio-chemotherapy with temozolomide in elderly patients with glioblastoma. A mono-institutional experience.

AIM: The aim of the present study was to evaluate the toxicity and clinical outcome of radio-chemotherapy with temozolomide in patients with glioblastoma aged more than 65 years. MATERIALS AND METHODS: The analysis was performed in 20 male and 20 female patients with a mean age at diagnosis of 71.2 (range=65-81) years, with Karnofsky performance status greater than 70 without important comorbidities. RESULTS: Toxicities related to temozolomide and concomitant radiochemotherapy were similar to those reported for younger patients. The median time to progression and median overall survival of the entire cohort, from the date of diagnosis, were 10.6 (range=6.7-14.4) months and 19.3 (range=17.8-20.7) months, respectively. No significant results for overall survival analysis were found for age at diagnosis and cardiovascular risk factors, as covariates, with hazard ratios of 1.00 (95% confidence interval=0.92-1.10) and 0.9 (95% confidence interval=0.43-1.88), respectively. CONCLUSION: Considering the relative good toxicity profile and the efficacy of treatment, our experience supports the use of radiochemotherapy with temozolomide in older patients with glioblastoma.