AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

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.

Impact of dose and volume on subcutaneous fibrosis.

The multifactorial genesis of radiation-induced fibrosis makes a general outline of the occurence of this late toxicity fairly unpredictable. Scientific knowledge about dose fractionation, irradiated volume, total time, conformation procedures including IMRT can help provide better treatments. Chemical and physical therapies aimed at the removal of fibrosis are still limited or under study. The system of monitoring late toxicity used by the authors is presented.

Concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, in recurrent endometrial cancer: a scoring system to predict clinical response and outcome.

AIMS AND BACKGROUND: This prospective, phase II study aimed to test the efficacy of concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, on the clinical outcome of a series of recurrent endometrial cancer patients and to determine the prognostic impact of a subset of factors. METHODS: Thirty patients with locally recurrent, nonmetastatic endometrial cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continous infusion, days 1-4; 1 g/m2/day; mitomycin C, 10 mg/m2, bolus iv, day 1). Nineteen patients (63.3%) underwent endocavitary, low-dose brachytherapy boost (20-25 Gy); eight patients (26.7%) received external beam radiation boost (14-20 Gy). RESULTS: Eleven complete responses (36.7%), 11 partial responses (36.7%), 6 disease stabilizations (20.0%) and 2 progressions (6.6%) were observed. After a median follow-up of 27 months (range, 1-108), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 46.8%, 35.2% and 41.2%, respectively. Two patients (6.7%) experienced hematological grade 3 toxicity. Two patients (6.7%) had grade 3 intestinal toxicity. Severe late toxicity was infrequent, only 3 patients showing severe vaginal stenosis (10.0%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin < 11 g/dL. With this device, it was clear that patients with a low score had a significantly better outcome (clinical remission: 77.2% of patients with a score < 2 vs 25.0% of patients with a score > or = 2, P = 0.009), better local control of the disease (50.2% vs. 0 at 3 years, P = 0.014,) and better overall survival (65.8% vs 0 at 3 years, P = 0.003). CONCLUSIONS: Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful in identifying patients with the best chance of benefiting from the treatment.

Biological optimization of the dose in pancreatic cancer.

In the last decades, many attempts were made to optimize the biological effect of RT in the treatment of pancreatic carcinoma. The use of combined radiotherapy and chemotherapy was certainly successful, with the most promising results achieved with the combination of several drugs with RT or with innovative modalities of administration of concomitant chemotherapy. A dose effect in resected tumors seems suggested by some studies; while the use of high doses in inoperable tumors did not result in significant advantages in terms of response and outcome, a significant correlation between dose and toxicity was observed. Altered fractionations were not studied systematically, though an accelerated-hypofractionated (30 Gy in 10 fractions) treatment is indicated as feasible in combination with concomitant chemotherapy with results similar to those achieved with conventional fractionations and a markedly shorter duration. Based on the small improvements recorded in the treatment of these tumors, the evaluation of newer treatment modalities seems justified.

Concomitant radiochemotherapy plus surgery in locally advanced cervical cancer: update of clinical outcome and cyclooxygenase-2 as predictor of treatment susceptibility.

OBJECTIVE: We have updated our findings on the efficacy of concomitant radiochemotherapy plus radical surgery in a larger series of patients (n = 54) with locally advanced cervical cancer (LACC). We also investigated the role of cyclooxygenase-2 (COX-2) in this clinical setting. METHODS: Radiotherapy was administered to the whole pelvic region (1.8 Gy/day, totaling 39.6 Gy) in combination with cisplatin (20 mg/m2) and 5-fluorouracil (1,000 mg/m2) (both on days 1-4 and 27-30). Radical surgery was performed 5-6 weeks after the end of treatment. RESULTS: A clinical complete or partial response was observed in all 53 evaluable patients (75.5 and 24.5%, respectively). At pathological examination, 23 of 51 patients (45.1%) undergoing radical surgery showed complete response to treatment, 18 patients (35.3%) only had microscopic residual disease, 6 patients (11.7%) had a partial response and 4 (7.8%) had no change in their disease. When logistic regression was applied, the FIGO stage (chi2 = 5.28, p = 0.021) and tumor to stroma COX-2 ratio (chi2 = 4.72, p = 0.029) retained an independent role in the prediction of the pathologic response to treatment. The 3-year disease-free survival (DFS) was 75.2%, with local relapse-free survival of 86.2% and metastasis-free interval of 89.9% at 3 years. Cases with a high COX-2 ratio showed a shorter DFS than cases with a low COX-2 ratio (p = 0.016). A direct association was shown between COX-2 ratio values and risk of recurrence, as assessed by Cox analysis using COX-2 ratio values as a continuous covariate (chi2 = 3.94, p = 0.047). CONCLUSION: This study confirms the possibility of achieving a very high rate of pathological responses in LACC patients administered chemoradiation plus surgery (3-year DFS 75.2%). Moreover, COX-2 status may play a role in the prognostic characterization and prediction of tumor response.

Incidental surgical findings of a phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with unresectable non-small cell lung cancer.

OBJECTIVE: to report the surgical facts of unresectable patients with locally advanced non-small cell lung cancer (NSCLC) treated in a phase I trial with concurrent weekly gemcitabine and radiotherapy who achieved a clinical downstaging so as to re-enter resectability. MATERIALS AND METHODS: from 3/99 to 11/00, 30 patients (ten stage IIIa, 16 IIIb and four IV) with histologically proven, unresectable NSCLC, were enrolled in this phase I trial. Gemcitabine was given weekly for 5 consecutive weeks as a 30-min intravenous infusion, at least 4 h before radiotherapy. Starting dose: 100 mg/m(2). Maximum tolerated dose (MTD): 350 mg/m(2). Radiotherapy total dose: 50.4 Gy (1.8 Gy/day) on primitive tumour and involved lymph nodes. RESULTS: 27 out of 30 patients (90%) were evaluable for clinical restaging (three patients who decided to continue their treatment elsewhere have been excluded). A major clinical response (partial+complete response) was observed in 17 out of 27 cases (62.9%). Clinical complete response rate was 3.7% (1/27) while partial response rate was 59.2% (16/27). Nine patients (33.4%) showed a clinical stable disease and one a disease progression (3.7%). Fourteen patients re-entered resectability and were operated upon: seven lobectomies; four bilobectomies; two pneumonectomies and one explorative thoracotomy. Mean operation duration time was 112 min; mean blood loss was 390 cc. Thirty-day morbidity and mortality were nil. Mean post-operative hospital stay was 6.8 days. A slight increase in operational technical difficulty was encountered. Definitive histology showed a pathologic downstaging of 71.4% (10/14). In four patients, only microscopic neoplastic remnants were found. CONCLUSIONS: combined treatment with weekly gemcitabine and concurrent radiotherapy is feasible. In patients with advanced NSCLC who achieved a good clinical response and therefore were judged to be resectable, surgery was possible without any increase in thirty-day morbidity and mortality. Satisfactory pathologic results were obtained.

Biological factors and therapeutic modulation in prostate cancer radiotherapy.

Biologic factors affect the ability of radiation to effectively treat all patients with prostate cancer. The use of prognostic and genetic markers (12 lipoxygenase, p53, bc1-2 genes, ploidy) may aid in the development of treatments for these patients. Particularly, several studies have shown that p53 tumor suppressor gene mutations are infrequent in prostate cancer and are associated with advanced disease. Recent efforts have been directed toward novel therapeutic modalities, especially in combination with standard irradiation of prostate carcinoma. These modalities are based on an improved knowledge of these biological factors involved in the progression and diffusion of the tumor, especially p53. Several authors evaluated the predictive and prognostic role of p53 in patients with prostatic cancer treated with radiotherapy. An extensive review of international reports on the subject is provided.