Stefano Pergolizzi

8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

BACKGROUND AND PURPOSE In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. MATERIALS AND METHODS Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). RESULTS A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p=0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. CONCLUSIONS Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

Prevention of radiation-induced diarrhea with the use of VSL#3, a new high-potency probiotic preparation

ditis. The time that elapsed between the upper endoscopy and the onset of fever (about 1 month) is also compatible with a typical incubation of a subacute endocarditis. Guidelines for prophylaxis in infectious endocarditis recommend antibiotic treatment before endoscopic procedures associated with high rates of bacteremia (esophageal dilation, variceal sclerotherapy, and laser therapy) in all patients, but also before therapeutic ERCP and percutaneous endoscopic gastrostomy in patients with lesions susceptible to endocarditis (heart valve diseases) (5). On the other hand, some studies have demonstrated that antibiotic prophylaxis can reduce the incidence of bacteremia, but it does not seem to prevent infectious postendoscopic endocarditis (6). We would recommend prophylactic therapy in all immune deficient patients with susceptible conditions even if they undergo low-risk endoscopic procedures. We hope that this prophylactic management can prevent infectious endocarditis, which is a potentially life-threatening disease.

Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: Review and recommendations of the supportive task group of the Italian Association of Radiation Oncology

PURPOSE Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia. MATERIALS AND METHODS The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts. RESULTS Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account. CONCLUSIONS In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer.

Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study.

PURPOSE Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to involve diffusely the lung. No agreement exists about whether diffuse bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose of this work is to evaluate the correlation between intrapulmonary spread of bronchioloalveolar carcinoma and its histologic and immunohistochemical characteristics. DESIGN Surgical specimens of 20 bronchioloalveolar carcinomas with radiologically proved evolution from focal to diffuse disease were retrieved and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR imaging examinations. Immunohistochemical studies were performed to investigate the expression of gelatinase A and alpha2-integrin. Correlation between immunohistochemical results and patterns of pulmonary spread was evaluated. Statistical evaluation was performed by using Fisher Exact Test. RESULTS Three histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11 cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were depicted radiologically: parenchymal opacification (11 cases), multiple nodules (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus none out of 8 non-mucin producing cancers developed parenchymal opacification. The difference was statistically significant (P<0.028). A statistically significant difference was also found between the development of parenchymal opacification and the level of alpha2-integrin: 11 out of 13 tumors with negative alpha2-integrin versus none out of 7 with positive alpha2-integrin immunoreactivity (P>0.033). CONCLUSIONS Diffuse bronchioloalveolar carcinoma may develop from a prior focal cancer. Mucinous subtype is the most prone to develop diffuse disease with parenchymal opacification, probably representing aerogenous spread. Low levels of alpha2-integrin receptors were found in bronchioloalveolar carcinoma which developed parenchymal opacification.

Unusual relapse of hepatocellular carcinoma

The authors report a patient with iatrogenic dissemination of hepatocellular carcinoma (HCC). A 65‐year‐old Caucasian man was found to have a moderately well‐differentiated HCC diagnosed by laparoscopy and biopsy; the patient had atypical left liver lobe resection. Thirty‐three months after definitive surgery a double relapse was found at the site of the previous laparoscopy and at the surgical scar; no other metastases were found. Surgical procedure for removal of these lesions was performed, and the patient received complementary radiation therapy. At 30 months of follow‐up, the patient is alive and disease free. The risk of neoplastic seeding through biopsy and improved safety in surgical techniques justify the omission of diagnostic biopsy in patients who have surgical procedures.

Mucositis in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus statements.

BACKGROUND Oral mucositis (OM) due to radiotherapy and systemic therapies in head and neck cancer treatment represents a major problem causing a wide spectrum of clinical signs and symptoms. This adverse event may reduce quality of life, resulting from debilitating oral pain, bleeding, dysphagia, infections, impairment of food intake, high rate of hospitalization and may interfere with the delivery of programmed treatment plans, ultimately jeopardizing patient outcome. Globally, there is a lack of evidence on effective measures for the prevention and treatment of OM, and only scant uniform conclusions and recommendations can be derived from the existing literature and guidelines. A multidisciplinary team of Italian head and neck cancer experts met in Milan 17-18 February 2013 with the aim of reaching consensus on prophylaxis and management of mucositis. The results of the literature review and the statements that achieved consensus are reported and discussed in this paper. MATERIAL AND METHODS The Delphi Appropriateness Method was used as a structured communication method for achieving consensus. Subsequently, external expert reviewers evaluated the conclusions carefully according to their area of expertise. RESULTS This paper presents 13 clusters of statements on prophylaxis and treatment of mucositis that achieved consensus. CONCLUSIONS OM represents a very stressful situation for head and neck cancer patients submitted to chemo-radiation or exclusive radiation treatment. A multidisciplinary approach is mandatory, but there is still no gold-standard protocol that is prominently better than others.

Prophylaxis of diarrhoea in patients submitted to radiotherapeutic treatment on pelvic district: personal experience

Diarrhoea is a severe side-effect of radiotherapy on the pelvic area. It is due to acute enteric damage. We aimed at determining the ability of a highly concentrated freeze-dried living bacteria compound (VSL/3) to reduce these side-effects in 190 patients receiving radio therapy on the pelvic area. A total of 95 patients received radiotherapy alone and 95 were also administered VSL/3 bags, at doses of one bag three times a day beginning on the first day of the radiotherapy treatment. The same diet was indicated for both groups. All patients were irradiated for 6 to 7 weeks, with Linac X-6 MV or 15 MV through a box multiportal technique with the lower limit of the fields below the obturator foramina, upper limit at L5-S1, lateral limit 1.5 cm beyond the innominate hip. The total radiated dose ranged from 60 to70 Gy for a daily dose of 180 cGy. Gastroenteric toxicity was rated in WHO degrees. Two patients receiving radiotherapy alone had to discontinue the treatment due to acute enteritis. Toxicity was found in 52 (50.6%) patients with radiotherapy alone vs 36 (30.5%) patients receiving VSL/3. None of them had to discontinue radiotherapy. Toxicity of degrees 3 or 4 was found in 28 patients receiving radiotherapy alone vs 7 with VSL/3. These preliminary data suggest the effectiveness of VSL/3 in preventing the occurrence of diarrhoea in patients submitted to radiotherapy with a direct and indirect improvement of their quality of life and a good tolerance.

Novel therapeutic approaches to cancer patients with bone metastasis.

Bone metastases are a common event in advanced cancer. Breast, lung, prostate and thyroid neoplasms have striking osteotropism. Bone metastatic cancer may be associated with catastrophic consequences for the patients. Therefore, new strategies are warranted in order to reduce the incidence of bone metastases and to palliative established skeletal disease. External beam radiation therapy, endocrine treatments, chemotherapy, bisphosphonates and radioisotopes are all important. Bisphosphonates have become the treatment of choice for tumor-induced hypercalcaemia and more recently they have been used alone or in combination with cytotoxic agents in the palliative treatment of patients with bone metastases. The results are encouraging. Currently, new bisphosphonates that are a hundred times more powerful with respect to clodronate and pamidronate are under investigation. The treatment of metastases to bone and mechanisms of pain relief after radiation therapy are poorly understood. Up to date, there are not standard criteria for the irradiation of bone metastases and bone pain relief may be reached using a variety of fractionation schemes. Radionuclide therapy is the systemic use of radioisotopes for bone pain. It is currently regarded as suitable for comparison with wide-field irradiation, but appears to have major disadvantages in terms of pain relief and toxicity.

Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group.

Performing intensity-modulated radiotherapy (IMRT) on head and neck cancer patients (HNCPs) requires robust training and experience. Thus, in 2011, the Head and Neck Cancer Working Group (HNCWG) of the Italian Association of Radiation Oncology (AIRO) organized a study group with the aim to run a literature review to outline clinical practice recommendations, to suggest technical solutions and to advise target volumes and doses selection for head and neck cancer IMRT. The main purpose was therefore to standardize the technical approach of radiation oncologists in this context. The following paper describes the results of this working group. Volumes, techniques/strategies and dosage were summarized for each head-and-neck site and subsite according to international guidelines or after reaching a consensus in case of weak literature evidence.

Use of diffusion-weighted, intravoxel incoherent motion, and dynamic contrast-enhanced MR imaging in the assessment of response to radiotherapy of lytic bone metastases from breast cancer.

RATIONALE AND OBJECTIVES To investigate the value of diffusion-weighted (DW), perfusion-sensitive, and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) techniques in assessing the response of bone metastases from breast cancer to radiotherapy, with particular emphasis on the role of intravoxel incoherent motion (IVIM)-DW parameters as a potential valuable imaging marker of tumor response. MATERIALS AND METHODS Fifteen women having breast cancer and bone metastases underwent MRI before and after radiotherapy (3 weeks [time 1], 2 months [time 2], and 4 months [time 3]), consisting of DW, perfusion-sensitive (IVIM), and DCE acquisitions. MR-based DW and perfusion parameters, including water diffusivity (D), perfusion fraction (f), pseudodiffusion (D*), total apparent diffusion coefficient (ADC-total), fractionated ADCs (ADC-high and ADC-low), and initial area under the gadolinium concentration curve after the first 60 seconds (IAUGC60), were determined. The morphologic MRI findings were also recorded. A one-way repeated measures analysis of variance was used to compare the value of MR-based parameters at the different time points. RESULTS A significant variation between pretreatment (time 0) and post-treatment (times 1, 2, and 3) was found for ADC-total and D parameters (P < .001). A statistically significant reduction was also found for IAUGC60 values between times 0 and 3 (P < .001). A significant change across the different time points was observed for D* and IAUGC60 parameters (P < .001). On the contrary, there was no statistically significant change over time for parameters ADC-total, D, f, and IAUGC60 comparing response between each metastasis, that is, the response to therapy was similar for each metastasis. CONCLUSIONS DW, IVIM, and DCE-MRI techniques show effectiveness in assessing the response to radiotherapy in bone metastases from breast cancer.