Role of multidimensional assessment of frailty in predicting outcomes in older patients with glioblastoma treated with adjuvant concurrent chemo-radiation.

BACKGROUND: Our aim was to evaluate the impact of comorbidities, clinical and biological factors on outcomes in elderly GBM patients treated with surgery followed by concurrent radiation (RT) and Temozolomide (TMZ). MATERIALS AND METHODS: Our sample includes 34 elderly patients with GBM who treated from January 2013 to December 2017. We collected data regarding age, extension of surgery, use of current medications, KPS, presenting symptoms, Prognostic Nutritional Index (PNI), Charlson Co-morbidity Index (CCI) and Frailty Index (FI). All of these parameters, measured before the start of RT-TMZ, were linked to clinical outcomes. RESULTS: With a median follow-up of 9.7 months, the median overall survival (OS) was 12.1 months and 1-year OS was 50%. In univariable analysis high KPS and total surgery were significantly associated with better OS. Also PNI, CCI and FI were a significant predictors of OS. At multivariate analysis KPS, type of surgery and FI remained a significant predictors of OS and, based on these parameters, we generated a prognostic score that, dividing patients into three risk categories, has proven to be a survival predictor, with an increase of the risk of death by 2.2 times for each increment of the score (HR 2.2, p = .0004). CONCLUSION: The appropriate management of elderly cancer patients with GBM is an important concern in oncology. Our data suggest that in elderly patients in good clinical conditions and with a low FI score, extensive surgery, when feasible without adding neurological impairment, followed by adjuvant RT-TMZ, should be considered.

Knowledge-based treatment planning: An inter-technique and inter-system feasibility study for prostate cancer.

PURPOSE: Helical Tomotherapy (HT) plans were used to create two RapidPlan knowledge-based (KB) models to generate plans with different techniques and to guide the optimization in a different treatment planning system for prostate plans. Feasibility and performance of these models were evaluated. MATERIAL AND METHODS: two sets of 35 low risk (LR) and 30 intermediate risk (IR) prostate cancer cases who underwent HT treatments were selected to train RapidPlan models. The KB predicted constraints were used to perform new 20KB plans using RapidArc technique (KB-RA) (inter-technique validation), and to optimise 20 new HT (KB-HT) plans in the Tomoplan (inter-system validation). For each validation modality, KB plans were benchmarked with the manual plans created by an expert planner (EP). RESULTS: RapidPlan was successfully configured using HT plans. The KB-RA plans fulfilled the clinical dose-volume requirements in 100% and 92% of cases for planning target volumes (PTVs) and organs at risk (OARs), respectively. For KB-HT plans these percentages were found to be a bit lower: 90% for PTVs and 86% for OARs. In comparison to EP plans, the KB-RA plans produced higher bladder doses for both LR and IR, and higher rectum doses for LR. KB-HT and EP plans produced similar results. CONCLUSION: RapidPlan can be trained to create models by using plans of a different treatment modality. These models were suitable for generating clinically acceptable plans for inter-technique and inter-system applications. The use of KB models based on plans of consolidated technique could be useful with a new treatment modality.

Detection of a second malignancy in prostate cancer patients by using [(18)F]Choline PET/CT: a case series.

BACKGROUND: The role of radiolabeled choline (Cho) in patients with biochemical recurrence after radical treatment for prostate cancer (PCa) is well established. Its widespread clinical use has prompted the depiction of incidentalomas, unusual sites of metastatic lesions, as well as false positive and negative cases. We reported a series of patients affected by biochemical recurrence of PCa imaged by [(18)F]Cho positron emission tomography/computed tomography (PET/CT) which resulted suspected for a second malignancy. CASE PRESENTATION: [(18)F]Cho PET/CT was performed in patients with biochemical PCa recurrence. From an internal clinical database we identified patients in which PET/CT resulted suspected for a second malignancy. A second malignancy was suspected in presence of "unusual" site of [(18)F]Cho uptake not consistent with clinical-instrumental history. Histology was used as reference standard for final diagnosis. Seven PCa patients (76 years, 71-84 years) with the suspicion of a second tumor based on [(18)F]Cho PET/CT findings were identified. Mean value of PSA at the time of [(18)F]Cho PET/CT was 2,37 ng/mL. The median time between PCa diagnosis and PET/CT was 6 years (range 0-14 years). In two cases history of a second malignancy (lung cancer and cutaneous basocellular carcinoma) was known (diagnosed 12 and 6 years after PCa, respectively). PET/CT identified 13 sites of [(18)F]Cho uptake (lung = 5, lymph node = 7, bone = 1). Final diagnosis was consistent with lung cancer in 5/7 cases (first diagnosis = 4/5, recurrence = 1/5), colorectal cancer and nodal metastases from melanoma in 1 case each. CONCLUSIONS: Although the clinical usefulness of Cho PET/CT for detecting cancer lesions other than prostate origin is known, for those patients who undergo this examination according to indication, the diagnosis of a second tumor has a significant impact on their therapeutic management.

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors.

PURPOSE: The objective of this study is to evaluate toxicity and cosmetic outcome in breast cancer patients treated with adjuvant hypo fractionated radiotherapy to the whole breast, and to identify the risk factors for toxicity. METHODS AND MATERIALS: Two hundred twelve women with early breast cancer underwent conserving surgery were enrolled in the study. The patients received 40.05 Gy in 15 daily fractions, 2.67 Gy per fraction. The boost to the tumor bed was administered with a total dose of 9 Gy in 3 consecutive fractions in 55 women. Physician-rated acute and late toxicity and cosmetic outcome (both subjective and objective) were prospectively assessed during and after radiotherapy. RESULTS: In our population study the mean age was 63 with the 17% (36 pts) of the women younger than 50 years.The median follow-up was 34 months. By the end of RT, 35 patients out of 212 (16%) no acute toxicity, according to the RTOG criteria, while 145 (68%) and 31 patients (15%) developed grade 1 and grade 2 acute skin toxicity, respectively.Late skin toxicity evaluation was available for all 212 patients with a minimum follow up of 8 months. The distribution of toxicity was: 39 pts (18%) with grade 1 and 2 pts (1%) with grade 2. No worse late skin toxicity was observed.Late subcutaneous grade 0-1 toxicity was recorded in 208 patients (98%) and grade 2 toxicity in 3 patients (2%), while grade 3 was observed in 1 patient only. At last follow up, a subjective and objective good or excellent cosmetic outcome was reported in 93% and 92% of the women, respectively. At univariate and multivariate analysis, the late skin toxicity was correlated with the additional boost delivery (p=0.007 and p=0.023). Regarding the late subcutaneous tissue, a correlation with diabetes was found (p=0.0283). CONCLUSION: These results confirm the feasibility and safety of the hypofractionated radiotherapy in patients with early breast cancer. In our population the boost administration was resulted to be a significant adverse prognostic factor for acute and late toxicity. Long-term follow up is need to confirm this finding.

Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7-9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. METHODS: We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. RESULTS: Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6-54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. CONCLUSION: Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient.

Short-course preoperative radiotherapy combined with chemotherapy in resectable locally advanced rectal cancer: local control and quality of life.

PURPOSE: The authors sought to evaluate the clinical outcome after preoperative short-course radiotherapy (SC-RT) for locally advanced resectable rectal cancer in terms of local control (LC) and quality of life (QoL). MATERIALS AND METHODS: Patients with locally advanced rectal cancer enrolled between 1997 and 2008 in an observational study of preoperative SC-RT were analysed. The treatment algorithm was neo-adjuvant chemotherapy (CT) administered for four cycles, followed by preoperative SC-RT administered 1 week after chemotherapy completion, delivering 20 Gy in five fractions over 1 week. Immediately in the following week surgery was performed. The adjuvant 5-FU-based CT was planned for pathological stage UICC≥II. LC, overall survival (OS), disease-free survival (DFS), early and late complications (RTOG scale) were analysed. All patients completed the EORTC QoL (C-30 and C-38), Faecal Incontinence QoL, and International Index of Erectile Function questionnaires (IIEF). RESULTS: A total of 67 patients were analysed. Chemotherapy and radiotherapy were well tolerated. At the pathological analysis, stable disease was obtained in 24 patients (36%), reduction of disease stage in 34 patients (50.7%), and progression in nine cases (13.3%). Adjuvant chemotherapy was indicated in 21 patients. Two locoregional recurrences, both within the radiotherapy volume, were observed, resulting in a 5-year LC of 97%. The 5-year DFS was 84%, with mean time to systemic progression of 24 months. After a mean follow-up of 114 months, the 5-year OS rate was 67%. Late toxicity >grade II was observed in 9% of patients. High anterior resection (AR) patients had significantly better scores than low AR or abdomino-perineal resection (APR). A total of 89% of the patients treated with conservative surgery had regular anal sphincter function. In male patients undergoing AR or APR, erectile dysfunction was found in 47% and 75% of the cases, respectively. CONCLUSIONS: Preoperative SC-RT combined with chemotherapy for locally advanced resectable rectal cancers was well tolerated. This treatment resulted in favourable LC, OS, low rates of toxicity and satisfying QoL.

Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: a 6 year single institutional experience.

OBJECTIVES: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. PATIENTS AND METHODS: Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥ 60, age ≥ 18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. RESULTS: All patients have completed the treatment protocol. Median age was 64.5 years (range 41-82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. CONCLUSIONS: The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.

Prostate embryonal rhabdomyosarcoma in adults: Case report and review of literature.

INTRODUCTION: Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, with a median occurrence age of 5 years, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethral obstruction, and systemic spread, commonly to the lungs, liver and bone. Several therapeutic approaches have been employed in the effort to treat prostate ERMS, but all of them have failed to gain a significant survival benefit in adult patients. CASE REPORT: We report on a case of a stage IV prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), and, subsequent radiotherapy to the prostatic bed (60 Gy/30 fxs). The patient remained free of progression of disease for about 1 year to finally experience a systemic relapse with multiple lung metastases and pleural effusion. The patient died for metastatic disease 27 months following the initial diagnosis. CONCLUSION: While it remains questionable which therapeutic approach for prostate ERMS in adults is the most appropriate, our report demonstrates that a chemo-radiation combined treatment can control the prostate disease, reducing the symptoms and improving the quality of life of these patients, for the most part destined to die for systemic progression of disease.