Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.

OLIGO-AIRO: a national survey on the role of radiation oncologist in the management of OLIGO-metastatic patients on the behalf of AIRO.

In the last years, several evidences demonstrated the role of stereotactic body radiotherapy (SBRT) in the oligometastatic disease and the possibility to increase survival in selected patients. In 2020 the study group "biology and treatment of the oligometastatic disease" of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey evaluating the attitude of physicians in treating the oligometastatic disease and the definition of it. An electronic questionnaire was administered online to the society members. 105 questionnaires were returned. 78% responders considered as oligometastatic a disease with ≤ 5 metastases. The majority of the responders (77%) treated > 50 patients in the last year, and 89% responders agreed in considering every oligometastatic tumor susceptible to local treatments. Regarding the clinical management of the oligometastatic disease, the majority of the responders (66%) suggested an interdisciplinary discussion. When choosing a treatment option for fit patients with a single oligometastatic focus, 52% of the responders agreed in proposing only SBRT. In the case of unfit patients with a single oligometastatic lesion the agreement was in favor of the SBRT alone (89%). In the oligoprogressive setting, 41% responders opted to continue the current systemic treatment and to add SBRT, while in the case of oligoresidual disease, 70% responders was in favor of adding SBRT and continuing the current systemic treatment. In conclusions, the survey illustrated the current agreement and prescribing attitude for oligometastatic patients in Italy. The non-homogenous agreement in some clinical scenarios suggest the need of more robust evidence.

What is the role of reirradiation in the management of locoregionally relapsed non small-cell lung cancer?

The prognosis of lung cancer patients has improved in the last few years. Despite definitive therapy, local recurrence or a second primary tumour can occur in many patients within previously irradiated areas. Recent developement of more accurate techniques in radiation oncology allows delivery of high radiation dose to the tumor with the aim of improving local control, delaying disease progression and in some cases even curing. Nevertheless, the use of high dose in the reirradiation setting is not without risks, especially when treatment volumes overlap with previously irradiated tissues. The risk of adverse effects must be balanced with the choice of an effective treatment by selecting suitable candidates and the best radiation technique. In this systemic review efficacy and toxicity of reirradiation in locoregionally recurrent non-small-cell lung cancer is extensively discussed. Results indicate that reirradiation might be beneficial in well-selected patients. Prospective and high quality studies are necessary in this field.

Post-mastectomy immediate breast reconstruction and adjuvant radiotherapy: long term results of a mono institutional experience.

INTRODUCTION: The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications. MATERIAL AND METHOD: All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50 Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors. RESULTS: Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59 months (range 6-142 months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively. CONCLUSION: This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.

Long term results of single high dose Stereotactic Body Radiotherapy in the treatment of primary lung tumors.

Stereotactic body radiotherapy (SBRT) is a standard treatment for inoperable early-stage NSCLC, with local control rates comparable to surgical series. Promising results have been achieved utilizing a high single-dose schedule. The aim of our study was to evaluate long-term local control and toxicity in a series of patients treated with SBRT delivered in a single dose of 30 Gy. 44 patients affected by early stage NSCLC were treated with SBRT delivered in a single dose of 30 Gy. Survival and prognostic factors were retrospectively evaluated. Median follow-up was 34 months (range 3-81). Three- and 5-year local progression-free survival (LPFS) were 87.8% and 87.8% respectively (median 30 months; range 6-81 months), 3- and 5-year OS and CSS were 64.9% and 36.9%, 80.9% and 65.5%, respectively. Two (4.6%) cases of grade 3 pneumonitis occurred. At the univariate analysis lesion diameter ≤ 25 mm was predictive of better 5-year LPFS (95.8% versus 56.3%; p = 0.003) and 5-year PFS (69.8% versus 27.8%; p = 0.002). The results of our study indicated a high local control, survival and tolerability after a long-term follow-up with the use of SBRT 30 Gy single dose. Further prospective studies could better define the role of this regimen.

Lactobacillus brevis CD2 for Prevention of Oral Mucositis in Patients With Head and Neck Tumors: A Multicentric Randomized Study.

BACKGROUND: Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. PATIENTS AND METHODS: A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. RESULTS: There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. CONCLUSION: Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.

Orbital Radiotherapy Plus Concomitant Steroids in Moderate-to-Severe Graves' Ophthalmopathy: Good Results After Long-Term Follow-Up.

BACKGROUND: Orbital radiotherapy (RT) is an effective and consolidate treatment for steroid-refractory Graves' ophthalmopathy (GO); however, long term effects are not well known. OBJECTIVES: The aim of this study was to evaluate the long term efficacy and toxicity of orbital RT plus concomitant systemic steroids in a population of patients with moderate-to-severe GO or with eyesight threatening symptoms refractory to steroids. METHODS: Forty patients with moderate-to-severe GO or with eyesight threatening symptoms not responsive/resistant to steroids were treated with orbital RT at the dose of 20 Gy in 10 fractions plus concomitant steroids. Clinical activity score (CAS) and symptoms status were evaluated to determine response to the treatment. RESULTS: We reported overall improvement of symptoms, in particular, a regression at 1-year of diplopia in 32.5% eye movement impairment in 42.5%, eyesight in 27.5% and a 2 point reduction in CAS. After a median time of 56 months 21.9% of the patients underwent orbital decompression for relapse of GO, 4.8% received surgical correction of strabismus, and 2.4% received eyelid lipectomy. Acute toxicity was mild; grade 1 - 2 keratitis occurred in 19.5% of the patients and grade 3 keratitis was observed in 2.4% of the patients. Cataract occurred in 7.4% of the patients after a median time of 24-month-follow-up. No secondary malignancies were reported. CONCLUSIONS: Our results reported the long-term efficacy and the good tolerance of orbital RT. The combination of RT plus steroids in this setting may avoid or delay performing the surgery in some cases.

Single nucleotide polymorphism of GSTP1 and pathological complete response in locally advanced rectal cancer patients treated with neoadjuvant concomitant radiochemotherapy.

PURPOSE: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. MATERIALS AND METHODS: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. RESULTS: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). CONCLUSION: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

Mono- and Bi-weekly Hypofractionated Radiation Therapy for the Treatment of Epithelial Skin Cancer in Very Elderly Patients.

BACKGROUND/AIM: Epithelial skin cancer frequently occurs in the elderly population, sometimes in an advanced stage, when intensive treatments are needed. Radiotherapy can achieve high response rates. We evaluated efficacy and tolerability of hypofractionated radiotherapy in a population of very elderly patients with locally advanced epithelial skin cancer. PATIENTS AND METHODS: Two different hypofractionated schedules were administered (21 patients): 6 Gy in 10 bi-weekly fractions (13 lesions) and 5 Gy in 12 bi-weekly fractions (13 lesions). Median age at treatment was 88 years, life expectancy was ≤5 years in 90.5%. RESULTS: The overall response rate was 96.1%, with 92.4% complete responses. All patients experienced an improvement of their symptoms and a reduction of pain and medication. The median overall survival time was 28 months (95% confidence interval=4.7-51.2 months). At the time of analysis, 52.3% of patients had died. CONCLUSION: Hypofractionated radiotherapy is an effective option of treatment, with low toxicity and optimal results, and can also be safely administered to these frail patients.

Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors.

Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.

Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

OBJECTIVES: To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. METHODS: Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. RESULTS: The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. CONCLUSIONS: Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy.

BACKGROUND: to evaluate the role of a risk stratification system in intermediate-risk prostate cancer (PCa) treated with hypofractionated radiotherapy (HyRT). METHODS: 131 patients affected by intermediate-risk PCa were treated with HyRT at the total dose of 54,75 Gy in 15 fraction plus 9 months of androgen deprivation therapy (ADT). Patients were classified as favourable risk (FIR) if they had a single NCCN intermediate-risk factor (IRF), a Gleason score ≤3 + 4 = 7, and <50 % of biopsy cores containing cancer (PBCC). If these criteria were not met were classified as unfavourable risk (UIR). Univariate and multivariate analyses using Cox proportional hazards model were calculated for biochemical recurrence-free survival (bRFS), the risk of local recurrence and metastasis-free survival (MFS). RESULTS: After a median follow-up of 56.7 months (range 9.8 to 93.7 months), 11 patients (8.4 %) died, of whom 2 (1.5 %) for PCa. In the univariate analysis, Gleason score, PPBCs, IRFs and PSA at first follow-up were prognostic factors for bRFS and LF while Gleason score, PPBCs and PSA at first follow-up were significant predictor for MFS. In the multivariate analysis only the PSA at first follow-up resulted a prognostic factor for bRFS and MFS. Patients with a value of PSA at first follow-up <0.7 ng/mL respect to those with PSA ≥0,7 ng/mL had a 5y-bRFS of 93.3 % vs. 57.5 %, 5y-MFS of 99.0 % vs. 78.9 % and 5y-LF of 5.8 % vs. 38.3 %. Patients in the UIR PCa group with a PSA value <0.7 ng/mL at first follow-up had significant better bRFS, LF and MFS. CONCLUSIONS: Risk factors currently not included in the guidelines are useful to stratify patients with intermediate-risk PCa in two groups of different prognosis even when HyRT is delivered. PSA at first follow-up is useful in UIR PCa to guide the overall length of ADT.

Renin-Angiotensin System Inhibitors Might Help to Reduce the Development of Symptomatic Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer.

INTRODUCTION: The purpose of the present study was to evaluate the role of renin-angiotensin system (RAS) inhibitors in preventing symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The data from 158 patients with a solitary lung lesion treated with 1 to 3 fractions of SBRT from December 2008 to July 2014 were retrospectively analyzed. The incidence of RP was evaluated according to the Common Toxicity Criteria for Adverse Events, version 4. The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) was analyzed to assess for possible correlations with the development of grade ≥ 2 RP. The patient and dosimetric variables were also assessed. RESULTS: After a median follow-up period of 13.8 months (range, 3.2-55.0 months), 22 patients had developed grade ≥ 2 RP. Patients with peripheral lesions, favorable dosimetric data, and ACEI and/or ARB use had a reduced risk of symptomatic RP. In unadjusted and adjusted multivariate analyses, ACEI and/or ARB intake and the dosimetric variables were statistically significant factors. In a secondary analysis, the use of ACEIs and ARBs among patients with a greater planning target volume and higher dosimetric values correlated with a reduced risk of symptomatic RP. CONCLUSION: The use of a RAS inhibitor was associated with a decreased incidence of symptomatic RP among patients undergoing SBRT for lung lesions. Patients with higher dosimetric values had a reduced risk of grade ≥ 2 RP with ACEI and ARB use.

Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1ß, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1ß, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Image-guided hypofractionated radiotherapy in low-risk prostate cancer patients.

AIM: To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT). METHODS: Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. RESULTS: The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥ 2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P = 0.04) in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P < 0.001) for HFRT patients. CONCLUSIONS: Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

Neoadjuvant chemoradiation with concomitant boost radiotherapy associated to capecitabine in rectal cancer patients.

PURPOSE: The primary end-points were complete pathological response and local control. Secondary end-points were survivals, anal sphincter preservation, and toxicity profile. METHODS: Patients with T3/T4 and or N+ rectal cancer (n = 65) were treated with preoperative concomitant boost radiotherapy (55 Gy/25 fractions) associated to concurrent chemotherapy with oral capecitabine. RESULTS: All patients completed the programmed treatment. The complete pathological response was achieved by 17 % of the patients. Anal sphincter preservation surgery was possible for 86 % of the patients with low rectal cancer (≤ 5 cm from the anal verge). The T-stage and N-stage downstaging were achieved by 40 and 58 % of the patients, respectively. Circumferential radial margin was involved (close/positive) in eight patients. After a median follow-up of 26 months, local and distant recurrence occurred in two and 11 patients, respectively. The 3-year overall survival and disease-free survival were 86.8 and 81 %, respectively. Non-hematological ≥ grade 3 toxicities were observed in 15 % of the patients. On univariate analysis N-downstaging and positive circumferential radial margin were significantly associated with worse overall survival (p = 0.003 and p = 0.023, respectively), disease-free survival (p = 0.001 and p = 0.036, respectively), and metastasis-free survival (MFS) (p = 0.001 and p = 0.038, respectively).On multivariate analysis, the N-downstaging were significantly associated with better overall survival (OS) (p = 0.022). CONCLUSIONS: Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Radiation treatment intensification may have a biological rationale; longer follow-up is needed.

Clinical outcomes of single dose stereotactic radiotherapy for lung metastases.

INTRODUCTION: Stereotactic body radiation therapy is an emerging noninvasive technique for the treatment of oligometastatic cancer. The use of small numbers of large doses achieve a high percentage of local control. The aim of this study was to evaluate the efficacy and tolerability of SBRT for the treatment of lung metastases in a cohort of patients treated between 2008 and 2012 at our institution. PATIENTS AND METHODS: A total of 66 patients with oligometastatic lung tumors (single pulmonary nodules in 40 patients; 61%) were included in the study. SBRT was performed with a stereotactic body frame and a 3-D conformal technique. Forty-nine central tumors received 23 Gy in a single fraction and 54 peripheral tumors received a dose of 30 Gy in a single fraction. The primary end point was local control; secondary end points were survival and toxicity. RESULTS: Median follow-up was 15 months (range, 3-45 months). Local control rates at 1 and 2 years were 89.1% and 82.1%, overall survival rates were 76.4% and 31.2%, cancer-specific survival rates were 78.5% and 35.4%, and progression-free survival rates were 53.9% and 22%, respectively. Median survival time was 12 months, and median progression-free survival time was 10 months. Toxicity profiles were good, with 2 cases of Grade 3 toxicity (pneumonitis). CONCLUSION: SBRT is an effective and safe local treatment option for patients with lung metastases, although it remains investigational; longer follow-up to confirm results is required.

Integral dose and radiation-induced secondary malignancies: comparison between stereotactic body radiation therapy and three-dimensional conformal radiotherapy.

The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/ß = 10 Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76 Gy(10)). Total NTIDs for both techniques was calculated considering α/ß = 3 Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.

Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: is it better than three dimensional conformal radiotherapy?

BACKGROUND: Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. METHODS: Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. RESULTS: Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs. CONCLUSIONS: In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

Late morbidity and oncological outcome after radical hypofractionated radiotherapy in men with prostate cancer.

OBJECTIVE: To test the hypothesis that three-dimensional hypofractionated radiotherapy (3D-HFRT) is well tolerated and not worse than 3-D conventional RT (3D-CRT) for oncological outcome. PATIENTS AND METHODS: In all, 162 men with hystologically confirmed prostate adenocarcinoma were included in the analysis. In all, 82 men were treated with 3D-HFRT (15 fractions of 3.62 Gy delivered 3 times/week; a total dose of 54.3 Gy). This group was retrospectively compared with 80 men who met the same inclusion criteria and who were treated with 3D-CRT (39 fractions of 2 Gy delivered daily; a total dose of 78 Gy). A short course of hormone therapy was administered concomitantly with the RT. RESULTS: Only one (1.7%) patient in the 3D-CRT group and two (4.0%) in the 3D-HFRT group had Grade 3 genitourinary toxicity. There was late gastrointestinal morbidity of ≥ grade 3 in only 5.1% of men treated with 3D-HFRT and in 4.0% of men treated with 3D-CRT. In both groups there was no Grade 4 toxicity. At the median (range) follow-up of 45 (39.4-51) months for the 3D-HFRT group and 57.5 (54.9-59.1) months for 3D-CRT group the progression rate was 18/82 (21.9%) and 20/80 (25.0%), respectively, with no significant worsening in the risk of biochemical failure (BCF; log-rank test, P= 0.222). CONCLUSIONS: In the present study, men with clinically localized prostate cancer had similar levels of morbidity irrespective of whether they received HFRT or CRT without any worsening in the early risk of BCF. Thus, the present data provide some clinical evidence to justify trends already emerging toward HF regimens for treating clinically localised prostate cancer.