Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIM: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. MATERIALS AND METHODS: This was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. RESULTS: Between March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14-35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7-152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. CONCLUSIONS: In our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.

Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma. Feasibility and tolerability in elderly and chemotherapy-ineligible patients.

INTRODUCTION: Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. We analyzed a group of patients treated at our institute with cetuximab plus volumetric modulation arc therapy (VMAT) with the RapidArc technique in a simultaneous integrated boost (SIB) regime. The primary end point was the assessment of acute toxicity and the feasibility of the combined approach. MATERIALS AND METHODS: Between December 2008 and March 2010, 22 patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities (the majority suffered of heart chronic diseases). All patients underwent planning CT (additional image modalities were acquired for contouring purposes in the same treatment position: MRI in 12 and FDG-PET in 4 out of 22 patients). VMAT, by means of RapidArc, and SIB with two dose levels of 54.45 Gy and 69.96 Gy in 33 fractions were adopted. All patients included in the analysis were concomitantly treated with cetuximab: administration of the drug was initiated 1 week before RT at a loading dose of 400 mg/m(2) body surface area over a period of 120 min, follow by a weekly 60 min infusion of 250 mg/m(2) for the duration of RT. Patients were assessed for toxicities according to the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: All but 2 patients completed treatment and achieved the minimum follow-up of 12 months after the end of the treatment. Of the 22 patients, 18% (4 patients) showed grade 1, 36% (8 patients) grade 2, and 36% (8 patients) showed grade 3 dermatitis, while 9% (2 patients) had grade 1, 36% (8 patients) grade 2, and 45% (10 patients) had grade 3 mucositis/stomatitis. No grade 4 toxicities were recorded. Considering blood parameters, 3 cases of grade 1 anemia and 1 case of grade 2 thrombocytopenia were observed. Nobody required feeding tube placement during treatment. CONCLUSION: The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.

Laparoscopic debulking of bulky lymph nodes in women with cervical cancer: indication and surgical outcomes.

OBJECTIVE: To describe the technique and the surgical outcome of laparoscopic resection of bulky lymph nodes before adjuvant treatment. DESIGN: Prospective pilot study. SETTING: Gynaecological oncology cancer centre. POPULATION: From January 2006 to February 2008, 22 consecutive women presented with cervical cancer and bulky metastatic lymph nodes (>2 cm). METHODS: All women underwent resection of bulky lymph nodes by laparoscopy. A prospective record of the main surgical outcomes was performed. MAIN OUTCOME MEASURES: Safety and efficacy of laparoscopic resection of bulky lymph nodes, conversion to laparotomy, intra- and perioperative morbidity. RESULTS: All the operations were completed by laparoscopy. Median operative time was 197 minutes (range 180-320). Median blood loss was 60 cc (range 10-100), two women experienced complications: one thermal injury of the sciatic root provoking postoperative leg palsy and one chylous ascites. The woman with the thermal injury has recovered most leg function with physiotherapy and the woman with chylous ascites recovered within 2 weeks, slightly delaying the adjuvant treatment. All women were discharged within 4 days from the operation (range 2-4). Pathology reports confirmed the presence of tumour metastases and the lymph nodes size. The adjuvant treatment started at a median time of 12 days (range 3-22). CONCLUSION: Debulking of large pelvic and para-aortic lymph nodes was effectively accomplished by laparoscopy in all 22 women with 9% complication rate. The surgical outcome is similar to historical series on women operated on by laparotomy, with the advantage of a faster recovery and an early start of adjuvant treatment.

Prognostic determinants in supraglottic carcinoma: univariate and Cox regression analysis.

BACKGROUND: A series of 281 consecutive patients affected by supraglottic cancer and treated with surgery alone or with surgery followed by radiotherapy between 1983 and 1989 was reviewed to identify significant prognostic determinants. METHODS: Fifty-one variables (related to host, tumor, and treatment) were tested by univariate and multivariate analysis performed on absolute and determinate survival. RESULTS: The final model of the multivariate analysis for absolute survival included the following covariates listed in order of higher relative risk of death: extracapsular spread, involvement of the medial wall of the pyriform sinus, thyroid cartilage invasion, metachronous tumor, anesthesiologic risk according to the American Society of Anesthesiologists classification (chi 2 = 71.28 with 6 d.f., p < .00001). The definitive model for determinate survival included: extracapsular spread, involvement of the medial wall of the pyriform sinus, extralaryngeal soft tissue invasion, and thyroid cartilage invasion (chi 2 = 82.74 with 5 d.f., p < .0001). CONCLUSIONS: Extracapsular spread was the most important factor affecting the prognosis of patients with supraglottic carcinoma. A second important finding was that T and N category did not emerge as a significant independent prognostic predictor at multivariate analysis. The negative impact on absolute survival of physical status and metachronous tumor could be the expression of the influence of concomitant diseases on survival. These observations concur to reinforce the concept that the current TNM classification is rather inadequate in predicting the prognosis of patients with supraglottic carcinoma when the aforementioned variables are considered.

Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics--a phase II multicenter study.

PURPOSE: A Phase II multicenter trial testing an accelerated regimen of radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry-derived tumor potential doubling time (Tpot). METHODS AND MATERIALS: From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinomas of the oral cavity and the oropharynx, with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction once a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day, with a 6-h interval, one of the two fractions being delivered as a concomitant boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy), shortening the overall treatment time to 4.5 weeks. A contemporary control group of 46 patients with Tpot of >5 days or unknown was treated with conventional fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy. RESULTS: All patients completed the accelerated regimen according to protocol and in the prescribed overall treatment time. Immediate tolerance was fairly good: 65% of the patients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to persist longer in AF than in CF patients. The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of the AF patients was 49.4%, while actuarial 2-year overall survival for the same patients was 43.5%. CONCLUSION: The results suggested that this accelerated regimen is worth testing in a controlled randomized trial to compare different accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA flow cytometry technique as a suitable method of evaluating tumor cell kinetics in multicenter clinical studies, on condition that all measurements are carried out by one most experienced laboratory.

Primary radiotherapy versus surgery and radiotherapy in the management of postmenopausal locally advanced breast cancer.

From 1978 through 1984, 103 postmenopausal patients with locally advanced breast cancer (T4 N1-2-3 MO) were treated by definitive radiotherapy (XRT, 35 patients) or mastectomy and postoperative radiotherapy (RM + XRT, 68 patients). A control group of 35 of the 68 RM + XRT patients was selected by matching several prognostic variables with the XRT group. Patients were followed for 4 to 10 years. At 5 years the probabilities of overall survival and relapse-free survival were 49.9% and 33.2% for XRT patients and 49.2% and 42.8% for RM + XRT patients, respectively (with no significant difference). The probability to remain free of local-regional progression at 5 years, with censoring of deaths, was 71.9% in the XRT group and 79.8% in the RM + XRT group. Of the patients treated with definitive radiotherapy, those who received 60 Gy or more to the primary tumor had a significantly better 5-year rate of local control: 88.0% vs. 68.0%, p less than 0.05. Our results suggest that adequate doses of radiotherapy can provide long-term local-regional control in a large proportion of survivors and can spare mastectomy in most patients, without however achieving substantial improvements in the poor survival results.

[Evaluation of the accuracy of the study on diverse techniques of planning radiotherapy of breast tumors]. / Valutazione dell'accuratezza nello studio con diverse metodiche del piano di trattamento radioterapico per tumori mammari.

The authors report the results of the analysis of several factors contributing to the accuracy of treatment planning in the radiation therapy of breast cancer. Different techniques (non-radiological vs CT-based) were used for the acquisition of patients' data; different methods (manual vs computerized) were employed for dose calculation. As for geometric parameters describing the external outline and target volume, mean differences were lower than 4%. Switching from a completely manual method to a CT-based one with computerized calculation, a 3.56% mean decrease in the value of reference isodose (p less than 0.01) was observed, together with a 3.87% mean increase in the estimated inhomogeneity (p less than 0.001). The non-CT-based outline of target volume exhibited geographic missing of inner portions of the target in 8/16 patients. Our results demonstrate that treatment planning procedures can be a significant source of clinically relevant inaccuracy, which may affect treatment outcome and tumor control.

[Treatment of pelvic recurrences of carcinoma of the cervix uteri by radiotherapy alone]. / Il trattamento radioterapico esclusivo delle recidive pelviche di carcinomi del collo uterino.

The best way to treat locally recurrent carcinoma of the uterine cervix has not been established. Our retrospective study refers to 37 consecutive patients, with recurrence in the pelvis, treated by radiotherapy alone. Thirty patients were treated by external beam therapy alone; intracavitary brachytherapy alone was adopted in 3 patients and a combination of both techniques in 4 patients. The total radiation dose exceeded 60 Gy in 62% of cases. A complete clinical response was observed in 54% of patients and a partial response in 32.4%. Overall crude survival was 70.3%, 28.9% and 23.2% at 1, 3 and 5 years respectively. In patients with recurrent tumors less than 40 mm in diameter a threefold 3-year survival was achieved (48.6% vs. 14.5%, p less than 0.025). With total doses higher than 60 Gy the 3-year survival resulted to be far better than with lower doses (39.1% vs. 10%, p less than 0.025). A significant advantage was also observed in the "complete responders" group (44% vs. 11.8%), but this difference can be explained by the link between response and the above-mentioned basic prognostic factors. Acute side effects and late complications were moderate and did not correlate with the type of primary treatment. A significant percentage (about 25%) of patients with locally recurrent cervix carcinoma may reach medium-term survival; better results can be achieved in selected groups with favourable prognostic factors and with adequate radiotherapeutic treatment.

Analysis of prognostic factors in patients with isolated chest wall recurrence of breast cancer.

A retrospective analysis of a series of 162 patients treated for isolated chest wall recurrence of breast cancer after mastectomy was undertaken. Cumulative survival, distant relapse-free survival, and freedom from local progression after 5 years from the diagnosis of recurrence were 34%, 28%, and 45% respectively. Five prognostic factors influenced survival: axillary node status, primary T stage, length of disease-free interval, and number and size of recurrences. Four prognostic factors influenced the local control: axillary node status, primary T stage, disease-free interval, and number of recurrences. Patients with three or more, out of five, favorable prognostic factors fared much better than those with two or less: 75% versus 15% survival at 5 years. Our findings suggest that it is possible to identify a group of patients with a distinctly good medium-term survival and local control of disease.

Reirradiation of recurrent head and neck cancers.

Ninety-nine patients with recurrent cancers of the head and neck region were treated with surgery, radiation therapy, or combination therapy. The follow-up period ranged from 18 months to 18 years. An initial overall complete response rate of 67% and a partial response rate of 7% (overall response rate-74%) were achieved. The eventual tumor control rate was 15%. Although equal initial response rates were achieved in recurrences at the primary site and the cervical nodes, the eventual local control was better for the former (21% vs. 10%). Patients receiving less than 5,000 rad radiotherapy had a 44% complete response and an 11% eventual tumor control. Patients receiving over 5,000 rad had an 80% complete response and a 25% eventual tumor control.

Radiation treatment with twice a day fractionation versus conventional fractionation in high grade astrocytoma. A retrospective study.

A consecutive series of 73 patients with high grade astrocytoma treated by surgery and postoperative radiotherapy was analysed. A total tumour dose of 60 Gy was delivered with either 2 Gy daily fractions (24 patients) or twice a day 1.5 Gy fractions, with a 4-hour-interval (49 patients). The analysis of survival with respect to patient variables showed that age and performance status were significant prognostic factors. As the type of fractionation was not randomly assigned, the comparison between the conventional schedule (CF) and the multifractionated schedule (MFD) was performed by means of a multivariate analysis adjusting for basic prognostic factors; CF proved to be significantly superior to MFD. The possible reasons for the disagreement between our results and the theoretical expectations in favour of MFD are discussed.

Proposed evaluation scale for damage to healthy tissues as a result of radiotherapy of chest, head and neck cancers.

The authors present, as a criterion of side-effect damage, an evaluation scheme based on the qualitative grading of the acute, intermediate and late effects of the therapeutic irradiation of chest, head and neck cancers. The choice of individual qualitative clinical criteria is complex and arbitrary, although the parameters used are currently found in the literature on radiotherapy. Nevertheless the classifications they have proposed, applied clinically in cases of head and neck cancers, have proved useful in assessing the risk factors of acute and late radiation effects according to the doses delivered. The gradings here described constitute a useful tool for the preliminary assessment of radiation damage and will facilitate the comparative analysis of different case series.

Vaginal molds for intracavitary curietherapy: a new method of preparation.

A new method of preparing vaginal molds for afterloading intracavitary brachytherapy is described. Our technique makes it possible to obtain the most accurate individualization of therapy as far as dose distribution is concerned by taking into account the patient's anatomy and target volume.

[A new method of planning and performing abdominal irradiation using the moving strip technic]. / Nuovo metodo di studio e di esecuzione dell'irradiazione addominale con "moving strip technique".

We make use of an individualized moving strip technique (MST) for ovarian cancer radiotherapy. On the pelvis, strip fields have smaller width than in usual MST proposed by Dembo and Delclos, and different heights. Femoral heads are spared without needing lead shields. Thus our technique can be useful for patients previously treated by heavy chemotherapy. Dosimetric checks by computer, TLD, and film dosimetry, show a fair dose homogeneity inside target volume.