[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice.

AIM: To evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice. BACKGROUND: Despite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies. MATERIAL AND METHODS: We reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated. RESULTS: 37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months. CONCLUSION: SIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.

Clinical Evaluation of Low-Molecular-Weight Hyaluronic Acid-Based Treatment on Onset of Acute Side Effects in Women Receiving Adjuvant Radiotherapy after Cervical Surgery: A Randomized Clinical Trial.

BACKGROUND: Radiotherapy treatment for cervical cancer (CC) often induces side effects, including inflammation, dryness, dyspareunia. Considering its key role in the healing process, hyaluronic acid (HA) could be useful for the completion of radiotherapy. OBJECTIVES: The aim of this work was to evaluate the ability of HA to reduce the onset of side effects due to radiotherapy. MATERIALS AND METHODS: In total, 180 women undergoing radiotherapy were randomized into two arms: controls and those treated with vaginal suppositories containing low-molecular-weight HA from day 1 of radiotherapy. The study lasted 5 weeks and was characterized by three visits: at baseline (T0), 15 days later (T1), and at the end of the radiotherapy cycle (T2). The onset of side effects, pain, safety, efficacy, acceptability of treatment, and compliance to the therapy were evaluated. RESULTS: Patients in the control arm reported the onset and worsening of all symptoms with a moderate or severe grade at T2, whereas in the treatment arm almost 90% of patients reported the absence of symptoms or a mild grade. All patients in the treatment arm referred a lower intensity of pain on a visual analog scale compared with the control arm at T2 (6.85 ± 0.94 vs. 1.88 ± 1.02). CONCLUSIONS: HA was able to help vaginal mucosa healing during radiotherapy in patients with CC.

Nodal Ratio as a Prognostic Factor in Patients with Four or More Positive Axillary Nodes Treated with Breast-conserving Therapy and Regional Nodal Irradiation.

AIM: This study aimed to investigate the prognostic value of the axillary lymph node ratio (i.e. positive axillary nodes to nodes removed) in patients with breast cancer treated with conservative surgery and regional radiotherapy. PATIENTS AND METHODS: We retrieved the records of 195 patients with breast cancer with pathological stage pT1-2 pN2-3, treated from January 2005 to December 2013 at our Radiation Oncology Centers; their clinical data were retrospectively evaluated. All patients underwent lumpectomy or quadrantectomy with axillary lymph node dissection, adjuvant chemo-with/without hormonal therapy and irradiation to the whole breast and ipsilateral axillary apex, infraclavicular and supraclvicular nodes, excluding internal mammary nodes. The primary end-point was to evaluate the nodal ratio as a prognostic factor; moreover, the following prognostic factors were evaluated: age, biological status and molecular profile. RESULTS: The median follow-up was 58 months (range=32-117.6 months). Two- and 5-year overall and recurrence-free survival rates were 96% and 88%, and 92% and 85%, respectively. On univariate analysis, factors influencing overall survival were nodal ratio >0.65 (p=0.033) and age (p=0.023); time to recurrence was detrimentally impacted only by Ki67 positivity ≥50% (p=0.049). At multivariate analysis, no significant associations were found. CONCLUSION: Adding irradiation to regional nodes after conservative surgery in patients with breast cancer with more than three positive axillary nodes does not alter the prognostic value of the nodal ratio, and we confirm this to be an important factor for predicting overall survival.

Breast cancer bone metastases: an epidemiologic study in selected radiation departments.

AIMS: To quantify radiation treatments for bone metastases from breast cancer in three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general population and the incidence and prevalence of breast cancer in this macro-area in a 8-year period. METHODS: All bone metastasis patients treated using radiotherapy in 8 radiation departments operating in the provinces of Messina, Catania and Ragusa were collected. Among these, metastases from breast carcinoma were analyzed according to year of irradiation. An analysis of breast cancer incidence and prevalence with respect to inhabitants in this macro-area was conducted using literature and census data. RESULTS: From January 2004 to December 2011, irradiation was delivered in 4419 bone metastasis patients. Among these, 1617 had a primary breast cancer with a median treatment per year of 206.5 (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004, there were 1,048,957 female residents in the three provinces and 1,065,422 in 2011. The reported breast cancer incidence and prevalence in Sicily was respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and 1091.29/100,000 in 2010. CONCLUSIONS: There has been an increase in both incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that there was no increment in skeletal-related events requiring irradiation in such patients in eastern Sicily radiation departments.

Diarrhoea in irradiated patients: a prospective multicentre observational study.

AIMS: To determine the incidence of cancer treatment-induced diarrhoea in patients submitted to irradiation. METHODS: Forty-five Italian radiation oncology departments took part in this prospective observational study and a total of 1020 patients were enrolled. The accrual lasted three consecutive weeks; evaluation was based on diary cards filled in daily by patients during radiotherapy and one week after cessation. Diary cards recorded both the onset and intensity of diarrhoea. RESULTS: A total of 1004 patients were eligible for this analysis. 147/1004 (14.6%) patients had diarrhoea. The median minimum number of daily events was 1 (range 1-7) with a median maximum events of 3 (range 1-23). 82/147 patients (56.2%) had a drug prescription for diarrhoea. In the evaluation of the onset of diarrhoea, in multivariate analysis, we found the following factors to be statistically significant predictors of an increased likelihood of diarrhoea: primitive tumour site, therapeutic purpose and field size. CONCLUSIONS: Patients with abdominal-pelvic cancer, treated with curative purpose and using large field sizes are at high risk of cancer treatment-induced diarrhoea. Diarrhoea was also observed in patients treated at other sites. In this population group there is the need for more stringent monitoring during the delivery of radiation therapy.

External beam irradiation in the palliation of bone metastases: a practice analysis among Sicilian Departments of Radiation Oncology.

BACKGROUND: In the treatment of bone metastases, the choice of radiation fractionation, total radiation dose, delivery technique, and imaging studies before treatment varies among radiation oncologists. Surveys on this issue, using case scenarios, have been published by groups from Europe, North America, and Australia-New Zealand. Our objective was to analyze retrospectively the "real" practice in nine radiotherapy centers located in Sicily. METHOD: A questionnaire including 17 items was distributed to 30 practicing radiation oncologists working in seven departments of four Sicilian cities (Messina, Catania, Ragusa and Palermo) during a meeting of the Sicilian Division of the Associazione Italiana Radioterapia Oncologica (AIRO). Participants were asked to answer the questions using a card for every patient treated with external beam irradiation from 1 January to 31 December, 2000. RESULTS: Six centers returned the questionnaires; 332 cards were valuable for a total of 5644 responses. All six responding departments used linear accelerators for treatment delivery. The most common dose fractionation was 30 Gy in 10 fractions and the most common technique used was opposed parallel local fields. Before the start of irradiation a bone scan was performed in 325 of the 332 (98%) patients treated and CT and/or MRI was performed in 320 (96%); surprisingly, standard roentgenograms were used in only 142 of 332 patients (42.8%). CONCLUSION: The "real" radiation practice for bone metastases in the region of Sicily confirms the results of the previously reported international surveys: there is a clear preference for fractionated treatment and local field therapy. The results of randomized studies, which demonstrated both the efficacy and the feasibility of a single 6-8 Gy fraction in the palliation of bone metastases, have little or no impact on the pattern of practice.

Muscle-invasive bladder cancer in elderly-unfit patients with concomitant illness: can a curative radiation therapy be delivered?

AIMS AND BACKGROUND: There is no standard treatment for elderly-unfit patients with muscle-invasive bladder cancer. Pelvic irradiation alone is an usual approach in this instance, and some reports have demonstrated that curative radiotherapy is feasible in elderly patients. To our knowledge, no data exist about the feasibility of a curative treatment in elderly patients with concomitant illness and a Charlson Comorbidity Index (an index of comorbidity that includes age) greater than 2. The main purpose of the present study was to establish the feasibility of irradiation in a cohort of elderly patients in poor general condition. METHODS: The records of 45 elderly-unfit patients (median age, 75 years; range, 70-85), with a comorbid Charlson score >2, treated with curative dose, planned continuous-course, external beam radiotherapy for muscle-invasive bladder cancer were reviewed. The patients were treated to a median total dose of 60 Gy (range, 56-64), with an average fractional dose of 190 +/- 10 cGy using megavoltage (6-15 MV). All patients were treated with radiation fields encompassing the bladder and grossly involved lymph nodes with a radiographic margin of at least 1.5 cm. RESULTS: No treatment-related mortality and clinically insignificant acute morbidity was recorded. No patient was hospitalized during or after the irradiation because of gastrointestinal or urogenital side effects. In one patient a week rest from therapy was necessary due a febrile status. Median survival was 21.5 months; overall 3- and 5-year survival was 36% and 19.5%, respectively. CONCLUSIONS: Elderly-unfit patients with comorbidities and >70 years of age can be submitted to radical pelvic irradiation. The results observed in this retrospective analysis have encouraged us to use non-palliative radiotherapy doses in these patients with muscle-invasive bladder cancer.