Performance status versus anatomical recovery in metastatic disease: The role of palliative radiation treatment.

Metastatic disease is a common complication of the most advanced malignancies. It may compromise the patients' quality of life, often posing a greater risk than the primary disease itself. Currently, several different therapeutic approaches are available to palliate or cure (single metastasis with primary neoplasm under control - radical surgery) secondary disease. In particular, radiation therapy is widely used, as it often leads to full or at least partial functional recovery, depending on the number and location of metastases. The aim of our study was to evaluate whether clinical improvement subsequent to radiation therapy may be related to anatomical recovery of the site of metastasis in cancer patients with metastatic disease. Given the heterogeneity of the diseases considered and the general complex conditions of the patients, a single method could not be used to evaluate the response to radiation treatment and its correlation with the performance status (PS). Thus, depending on the specific disease being assessed, we divided the patients into different groups. Patients in the same group were followed up with the same methods. This correlation was noted in a very high percentage of patients, predominantly in patients with vertebral and brain metastases. Moreover, we investigated the use of magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) in the study of spinal metastases. We propose its use in the local evaluation of vertebral secondary lesions, both in the diagnostic phase and during the assessment of treatment efficacy.

Adjuvant chemoradiotherapy in gastric cancer: a pooled analysis of the AIRO gastrointestinal group experience.

BACKGROUND: Given the poor compliance with adjuvant chemoradiotherapy (CRT) in gastric cancer reported in previous studies, a survey was conducted among 18 Italian institutions within the AIRO Gastrointestinal Group to investigate current treatment modalities, toxicities, and compliance with adjuvant CRT. PATIENTS AND METHODS: Data from 348 patients operated on for gastric cancer were collected retrospectively from September 2000 to June 2008 and analyzed. The adjuvant treatments included CRT according to center guidelines. In multivariate analysis, acute hematological, gastrointestinal, and renal toxicity (according to the RTOG Acute Radiation Morbidity Scoring Criteria) and compliance with treatment were studied, as well as risk factors for local control, metastasis-free survival, disease-free survival, and overall survival. RESULTS: Compliance with treatment was excellent: 95.7% of patients completed CRT. During CRT, acute G3-G4 ­hematological toxicity was 3.7% and acute G3-G4 gastrointestinal toxicity 4%. 78.4% of patients completed chemotherapy (CT), either before or after CRT. During CT acute G3-G4 hematological toxicity was 5.4% and acute G3-G4 gastrointestinal toxicity 6%. Overall, 74.1% of patients completed the prescribed treatment (CRT and CT). Doses greater than 4500 cGy did not compensate for more aggressive disease. The 5-year overall survival was 51%. CONCLUSIONS: The adjuvant treatment of gastric cancer within the AIRO group was diverse, but radiotherapy treatment was homogeneous (in terms of technique) and well tolerated. Toxicity was low and compliance with treatment was good during CRT; these results may be due to the radiotherapy technique applied. This survey could be used as a benchmark for further studies.

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams.

BACKGROUND AND PURPOSE: The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. MATERIALS AND METHODS: A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. RESULTS: All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. CONCLUSIONS: The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy.

Solitary plasmacytoma of the larynx treated with radiotherapy: a case report.

AIMS AND BACKGROUND: Solitary plasmacytomas are rare tumors accounting for less than 10% of plasma cell neoplasms. On initial presentation they must be differentiated from multiple myeloma. This can be difficult because a high percentage of these tumors may be associated with subsequent development of multiple myeloma. We present a case of plasmacytoma of the larynx treated with surgery and radiotherapy. CASE REPORT: A 56-year-old man presented a solitary plasmacytoma of the larynx. The diagnosis was made by biopsy and the presence of a mass on the right side of the larynx was confirmed by computed tomography and whole-body positron-emission tomography. Soon after the biopsy the patient underwent a CO2 laser cordectomy. After the definitive histological confirmation, the patient was referred to our department for three-dimensional conformal radiotherapy (3DCRT) to the involved site with curative intent. The prescribed dose was 50 Gy. RESULTS: Five months after the 3DRTE treatment there was no CT or PET evidence of tumor, and examination by the otorhinolaryngologist confirmed the success of laser cordectomy and 3DRTE treatment. There were no long-term side effects of the treatment. CONCLUSION: Radiation therapy following CO2 laser cordectomy can achieve excellent locoregional control of solitary plasmacytoma of the larynx.

Skin toxicity from external beam radiation therapy in breast cancer patients: protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor®).

INTRODUCTION: This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer. MATERIALS AND METHODS: 71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship. RESULTS: Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68). CONCLUSIONS: The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

The INTER-ROMA project--a survey among Italian radiation oncologists on their approach to the treatment of bone metastases.

AIMS AND BACKGROUND: Radiotherapy has an established palliative role for bone metastases but despite the large number of patients treated there is still controversy surrounding the optimal radiotherapy schedule to prescribe. The aim of this survey was to determine the decision patterns of Italian radiation oncologists in four different clinical cases of patients with bone metastases. METHODS AND STUDY DESIGN: During the latest national meeting of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to attending radiation oncologists. The cases were different with respect to the histology of the primary tumor, performance status, pain before and after analgesics, tumor site, and radiological characteristics of the metastatic lesions. For each clinical case the respondents were asked to give an indication for treatment; prescribe doses, volumes and treatment field arrangements; decide whether to prescribe prophylactic supportive therapy or not; and provide information about factors that particularly influenced prescription. Finally, a descriptive statistical analysis was performed. RESULTS: Three hundred questionnaires were distributed to radiation oncologists attending the congress. One hundred twenty-five questionnaires were returned but only 122 (40.6%) were adequately completed and considered for the analysis. Considerable differences were observed among radiation oncologists in prescribing and delivering radiotherapy for bone metastases. There was also a notable divergence from international guidelines, which will be discussed in this report. CONCLUSIONS: Despite the results of clinical trials, Italian radiation oncologists differ considerably in their decisions on treatment doses and volumes. National guidelines are needed in order that patients can be treated uniformly and better data will become available for evidence-based palliative radiotherapy.

Prevention of cutaneous damages induced by radiotherapy in breast cancer: an institutional experience.

BACKGROUND AND AIMS: A minimal part of patients treated with radiotherapy on the entire breast may present an acute, subacute or chronic cutaneous damage of the healthy tissues involved in the radiation fields. The aim of this retrospective study was to evaluate the most efficient topical hydrating treatment in the prevention of cutaneous radio-induced acute effects in breast cancer. MATERIAL AND METHODS: From February 2009 to March 2010, 100 patients affected by breast cancer have been recruited, all of the female sex and with an average age of 47 years. The following topical treatments were compared: Pure vitamin E (Vea lipogel®), Omega-3,6,9 (Quinovit®), Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A.s-I-M.t-O.dij, (Ixoderm®), natural triglycerides-fitosterols (Xderit®). All enrolled patients were subjected to breast conservative treatment (quadrantectomy with or without homolateral axillary dissection) and without prosthesis positioning, in combination or not with hormonal treatment. Evaluation of the cutaneous acute toxicity was defined according to the RTOG scale either during radiotherapy and during follow-up (3 months after radiation treatment). RESULTS: All patients completed the radiotherapy; 62% of patients presented G0-G1 cutaneous toxicity, 28% have developed G2 cutaneous toxicity, 10% have developed G3 toxicity; no patient presented G4 toxicity. Analysis of the data revealed a correlation between the topical treatment used and the incidence of cutaneous toxicity. CONCLUSIONS: Of the patients who used the cutaneous hydrating creams--betaglucan, sodium hyaluronate (Neoviderm®) and Vitis vinifera A.s-I-M.t-O.dij (Ixoderm®)--during the radiation treatment, 80% developed G0-G1 toxicity and 20% G2 toxicity. The patients who used the other hydrating creams tested in the study manifested not only G1-G2 toxicity but also some G3 toxicity. Chemotherapeutic treatment with taxanes and/or anthracyclines did not result in an increased breast cutaneous toxicity induced by radiotherapy. The hormone therapy given to patients undergoing radiotherapy did not result in increased breast cutaneous toxicity. Further analysis on a larger number of patients is necessary for definitive results.

Outcomes of radiation therapy for T1 glottic carcinoma from an Italian regional series with doses ranging from 60 to 66 Gy.

AIMS AND BACKGROUND: Radiotherapy has remarkable success rates for the cure of patients affected by glottic carcinoma; local control rates are similar to surgery with lower morbidity and better functional results. Our aim was to determine local-regional control rates, overall survival, second cancer incidence, acute-late toxicity and prognostic factors in our series of T1 glottic cancer patients with radiation doses of 60 to 66 Gy. Functional results were not sufficient for statistical analysis. METHODS AND STUDY DESIGN: A retrospective study was carried out of all T1N0 glottic carcinomas treated with radiation therapy between 1996 and 2006. To be eligible, patients had to have newly diagnosed cancer and had to be treated with a curative intent by radiation therapy alone. Ninety-eight patients satisfied the eligibility requirements: 85 patients had T1a disease; 13 patients were staged as T1b. Treatment was performed for all cases with a 6 megavoltage linear accelerator. The total dose prescribed varied from 60 to 66 Gy: 2 Gy/fraction, 1 fraction/day, 5 fractions/week. During treatment, a weekly clinical evaluation was performed; endoscopic examination was performed once every two weeks. After the treatment, a clinical, endoscopic and radiological follow-up was performed every three months for the first two years, every 6 months till the fifth year, and then once a year. RESULTS: With a median follow-up of 41.5 months (range, 10-132; mean, 56.8), we registered 12 cases of local failures; 8 of them were successfully treated with salvage surgery (median time to relapse, 3-48 months). The local relapse rate was 12.2%, and disease-specific survival, taking into account salvage surgery, was 6%. Thirty-four deaths were registered: 2 for local progression, 2 for distant metastasis, 4 for a new primary cancer, and 26 for non-neoplastic causes. Five- and 10-year overall survival were respectively 85.8% and 69.4%. Four cases of lung cancer were detected in the upper aerodigestive tract in our series. In terms of acute-late toxicity, no grade 3-4 dermatitis, dysphagia or hoarseness occurred. Mild dermatitis and arythenoid edema were the most common causes of toxicity. Only one patient did not complete the treatment (60 Gy instead of the planned 66 Gy). CONCLUSIONS: Our series confirmed the primary role of radiation therapy for the cure of T1N0 glottic cancer. Outcomes were good in terms of local-regional control as well as overall toxicity. Radiation therapy can be offered to T1 glottic cancer patients as a valid alternative to surgery, with high rates of functional preservation.

Late toxicity in Wilms tumor patients treated with radiotherapy at 15 years of median follow-up.

BACKGROUND: We report the radiation-induced late morbidity observed in our prospective series of Wilms tumor patients treated at the Second University of Naples. METHODS: From April 1981 to April 2000, 98 patients were referred at our institution for treatment of Wilms tumor. Among them, 51 underwent radiotherapy and 34 patients had a minimum follow-up of 5 years. Doses of irradiation and treatment portals were those recommended by the guidelines of the Italian Association of Haematology and Paediatric Oncology according to risk stratification. All eligible patients were reviewed for follow-up every 6 months. Median follow-up was 181 months (range 60 to 264 months). RESULTS: Eleven out of 34 patients (32%) did not suffer from any significant late side effect. Out of the remaining 23 (68%), 14 (41%) suffered from scoliosis presenting between 60 and 180 months from completion of treatment. Muscular hypoplasia, length inequality, kyphosis, and iliac wing hypoplasia were seen respectively, in 4 (12%), 4 (12%), 5 (15%), and 3 (9%) patients. The incidence of intestinal occlusion was 20%. One patient had chronic renal insufficiency. Four out of 13 female patients reported ovarian failure. Three out of the 7 patients who had radiotherapy to the lung developed radiation-pneumonitis. Radiation-induced heart disease was seen in 3 (9%) patients. Three patients (9%) suffered from second malignancies arising within the irradiated volume. CONCLUSIONS: Our data confirm the high incidence of late radiation morbidity in patients undergoing adjuvant radiotherapy for Wilms tumor. For most organ systems there is a correlation between total dose, morbidity rates, and degree of severity.

Adjuvant chemoradiotherapy in patients with stage III or IV radically resected gastric cancer: a pilot study.

BACKGROUND: Adjuvant chemoradiotherapy does not represent the standard of care in patients with resected high-risk gastric cancer; however, results from phase 2 and randomized trials suggest improvement in overall survival. We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer. DESIGN: Pilot study. SETTING: University hospital. PATIENTS: Twenty-nine patients with T4N+ or any TN23 gastric cancer previously treated with potentially curative surgery were enrolled. All of the patients received combined adjuvant chemotherapy with FOLFOX-4 (ie, a combination of folinic acid [leucovorin], fluorouracil, and oxaliplatin [Eloxatin]) for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy was begun after the first 2 cycles of FOLFOX-4, which was reduced by 25% during the period of concomitant radiotherapy. MAIN OUTCOME MEASURES: Treatment toxic effects according to the National Cancer Institute-Common Toxicity Criteria classification, overall and disease-free survival rates, and identification of prognostic indicators. RESULTS: All of the patients completed treatment. Severe hematologic and gastrointestinal toxic effects occurred in 10% and 33%, respectively. No acute hepatic or renal toxic effects were observed; 1 patient experienced severe neurotoxicity. Disease-free and overall survival rates at 1, 2, and 3 years were 79%, 35%, and 35% and 85%, 62.6%, and 50.1%, respectively, and were shown to be substantially better than those observed in untreated patients. Long-term outcome was related to TNM stage, basal serum tumor marker level, and, particularly, lymph node ratio. CONCLUSION: A multimodal approach with FOLFOX-4 and radiotherapy is feasible and effective for the treatment of patients with resected high-risk gastric cancer.

Multimodality treatment of locally advanced soft-tissue sarcomas of the extremities.

BACKGROUND: Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment of locally advanced soft tissues sarcomas of the extremities. Moreover the employment of combined modalities in locally advanced soft tissues sarcomas of the extremities allow to maximize the chance of local cure even in difficult presentation cases, and possibly improve survival, especially in high-risk disease patients. In patients with sarcomas of the extremities in which definitive surgery has not been radical (with positive or "close" margins) radiotherapy can improve the results in terms of Disease Free Survival (DFS) and, together with chemotherapy, of Overall Survival (OS). We recommend radiotherapy in case of deep tumor location, inadequate surgical margins and grade 3 tumour; for positive or "marginal (or close)" excision (that means inadequate surgery) or in selected patients with a bad prognosis, we believe that a multidisciplinary approach can be preferable. INTRODUCTION: Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment. In patients with sarcomas of the extremities in whom definitive surgery has been or not radical (positive or "close" margins), radiotherapy with chemotherapy can improve the results in terms of Disease Free Survival (DFS) and Overall Survival (OS), while RTE alone seems to improve local control. MATERIALS AND METHODS: From 1/2000 to 12/2005 we treated 34 patients affected by locally advanced sarcomas of the upper or lower extremities with radiotherapy (doses ranging from 54 to 66 Gy) and chemotherapy in 18/34 with an adjuvant scheme that consisted in Epirubicine (120 mg/m(2)) plus Ifosfamide (7000-9000 mg/m(2)). RESULTS: Disease Free Survival (DFS) and the Overall Survival (OS) rates were 76% and 82%, respectively. Eighteen patients developed one or more long-term side effects. Most of these complications were mild: all patients experienced only erithema, edema, local sclerosis or moderate pain. CONCLUSION: Radiotherapy has an important role as a post-operative treatment also when surgery was non-radical. It improves local control more in patients with high-grade sarcomas of the extremity with positive or close margins. It is still difficult to assess the role of adjuvant chemotherapy.

Scintigraphic evaluation of oesophageal transit during radiotherapy to the mediastinum.

BACKGROUND: To quantitatively evaluate radiation-induced impaired oesophageal transit with oesophageal transit scintigraphy and to assess the relationships between acute oesophagitis symptoms and dysmotility. METHODS: Between January 1996 and November 1998, 11 patients affected by non-small-cell carcinoma of the lung not directly involving the oesophagus, requiring adjuvant external beam radiotherapy (RT) to the mediastinum were enrolled. Oesophageal transit scans with liquid and semisolid bolus were performed at three pre-defined times: before (T0) and during radiation at 10 Gy (T1) and 30 Gy (T2). Two parameters were obtained for evaluation: 1) mean transit time (MTT); and 2) ratio between peak activity and residual activity at 40 seconds (ER-40s). Acute radiation toxicity was scored according to the joint EORTC-RTOG criteria. Mean values with standard deviation were calculated for all parameters. Analysis of variance (ANOVA) tests and paired t-Tests for all values were performed. RESULTS: An increase in the ER-40s from T0 to T1 or T2 was seen in 9 of 11 patients (82%). The mean ER-40s value for all patients increased from 0.8306 (T0) to 0.8612 (T1) and 0.8658 (T2). These differences were statistically significant (p < 0.05) in two paired t-Tests at T0 versus T2 time: overall mean ER-40s and upright ER-40s (p = 0.041 and p = 0.032, respectively). Seven patients (63%) showed a slight increase in the mean MTT value during irradiation but no statistically significant differences in MTT parameters were found between T0, T1 and T2 (p > 0.05). CONCLUSION: Using oesophageal scintigraphy we were able to detect early alterations of oesophageal transit during the third week of thoracic RT.

Dose and volume impact on radiation-induced xerostomia.

Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.

When can a drug be considered synergic with radiotherapy?

The combination of radiotherapy with chemotherapy is now considered the standard treatment for a number of tumors. However frequently, within radiotherapy as well as medical oncology, considerable skepticism has been expressed about the real impact of this therapeutic modality, in spite of the improvement in terms of outcome seen in numerous trials concerning head and neck, lung, esophageal cancer and tumors of the anal canal, the uterine cervix and pancreas. Considering the evident clinical advantages achieved in the last 2-3 decades, a close collaboration between basic, preclinical and clinical research is desirable to further optimize the outcomes based on the present radiobiological knowledge. As for the preclinical evaluation different methods should be concomitantly used to analyze the pharmacokinetics and mechanism of action; the method of tumor growth delay should be used especially in neoadjuvant clinical settings; the method of tumor control should be used when chemoradiation is aimed at the local cure of the patient independently of subsequent surgery.