The 2022 Assisi Think Tank Meeting: White paper on optimising radiation therapy for breast cancer.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy.

BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

Results of hypofractionated whole brain radiotherapy (2×8 Gy) for patients with brain metastases from lung cancer.

PURPOSE: To evaluate the clinical and radiologic response rates, toxicity and tolerability of 2×8 Gy whole brain radiotherapy (WBRT) in lung cancer patients with brain metastases (BM). METHODS: WBRT was delivered to 126 lung cancer patients with BM during 2002-2006. External beam RT was delivered with a fraction dose of 8 Gy on the same day of each consecutive week. Tumor and symptom response and toxicity were recorded at every follow-up. Recursive partitioning analysis (RPA) and the new Graded Prognostic Assessment (GPA) were used for analysis of overall survival (OS). RESULTS: Twenty-three patients had small cell (SCLC) and 103 had non small cell lung cancer. Pretreatment median Karnofsky performance score (KPS) was 70 (range 20-90). Clinical response rates were as follows: complete 31%; good partial 30.2%; partial 21.4%; stable 7.9%; and progressive 5.6%;. Median palliation and survival duration was 57 and 80 days, respectively. Two- and 6-month survival rates (SR) were 59.5% and 25.4%, respectively. According to recursive partitioning analysis (RPA) 6- month SR for groups 1, 2 and 3 were 61.5, 41.6 and 33.9%, respectively (p=0.002). Six-month SR for the new Graded Prognostic Assessment (GPA) were: GPA 0-1, 7%; GPA 1.5- 2.5, 34.2%; GPA 3, 25%; and GPA 3.5-4.0, 66.6% (p=0.0003). CONCLUSION: 2×8 Gy WBRT was found to be feasible. However, the late morbidity of this schedule is unknown so its use could be restricted to patients with poor performance status, with a short life expectancy and/or social problems, unlikely to tolerate more protracted radiotherapy regimens.

Erythropoietin and radiotherapy in lung cancer patients.

PURPOSE: To evaluate the effectiveness of recombinant human erythropoietin (rhEPO) in relation to low hemoglobin (Hb) level, overall tumor response rates, and rhEPO adverse events in patients with lung cancer undergoing radiotherapy (RT). PATIENTS AND METHODS: Thirteen consecutive patients were included. All of them had measurable tumor before RT. 150 IU/kg of rhEPO-alpha or -beta were administered 3 times per week, 7-10 days before RT. The target Hb value was 13 g/dl. Tumor response was assessed 6 weeks after completion of RT. RESULTS: Response to rhEPO was seen 62% (n=8) of the patients. Weekly mean Hb increment was 0.69 g/dl (range 0.42-1). The mean Hb value during RT was 13.2 g/dl (range 9-14.7) in responding patients, and 10.7 g/dl (range 9.7-11.8) in non-responding patients (p=0.005). Overall response rates to RT were significantly higher in responding than in non-responding patients (p=0.034). CONCLUSION: rhEPO increased Hb levels in lung cancer patients undergoing RT. However, safety, and more importantly, indications need further clarifications.

Postoperative radiotherapy in intermediate and high-risk Stage I endometrial cancer: analysis of prognostic factors and survival.

PURPOSE: Patients with Stage IA Grade (G) III, Stage IB GII-III and Stage IC GI-II-III endometrial cancer who received postoperative adjuvant radiotherapy were evaluated in terms of local control, disease-free and overall survival rates and prognostic factors. MATERIALS AND METHODS: Four hundred and three patients with Stage I endometrial cancer treated with radiotherapy from January 1990 to December 2003 at Ege University Faculty of Medicine Department of Radiation Oncology were reviewed retrospectively. According to our radiotherapy protocol patients with Stage IB G2 disease (149 patients) received only external radiotherapy and the remaining (254 patients) received both external radiotherapy and intracavitary brachytherapy. RESULTS: Median age of the patients was 58 (range: 37-83). Nine patients (2.2%) had Stage IA, 196 (48.6%) had Stage IB and 198 (49.1%) had Stage IC disease. Histologic grade was 1 in 52 (12.9%) patients, 2 in 268 (66.5%) patients and 3 in 83 (20.6%) patients. Seventy-one (17.7%) patients had lymphovascular space invasion. Five-year locoregional relapse-free, distant-free, disease-free survival (DFS) and overall survival (OS) were 98.2%, 92.8%, 91.8% and 87.7%, respectively. In multivariate analysis, myometrial invasion and lymphovascular invasion were predictive factors for DFS and for OS prognostic factors were histologic type, myometrial invasion, and histologic grade. During radiotherapy 47.9% of the patients developed acute morbidity and 26.3% developed late morbidity, vaginal stenosis being the most frequent late morbidity. CONCLUSION: Postoperative adjuvant radiotherapy provides high locoregional control rates with acceptable toxicity in selected patients with Stage I endometrial carcinoma.

The role of surgery and fluoroquinolones in the treatment of multidrug-resistant tuberculosis.

SETTING: Although modern tuberculosis treatment relies on chemotherapy, surgery is accepted as adjuvant treatment for multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate the effect of resectional surgery and fluoroquinolones on long-term treatment success and survival in a large group of MDR-TB cases. DESIGN: A total of 252 patients with MDR-TB were included in this retrospective cohort study. Multiple logistic regression was used to determine independent predictive factors for long-term treatment success, and survival analyses were done based on different treatment approaches with or without surgery. RESULTS: The mean age of the study cohort was 37.9 +/- 12.5 years; 204 (80%) were males. Long-term treatment success was associated with resistance to fewer drugs, female sex, younger age and limited disease. Sixty-six patients (26.2%) had undergone resectional surgery after 2-16 months of treatment. The highest long-term treatment success and survival rates were achieved in patients who both received fluoroquinolones and underwent surgery (P = 0.001 vs. other groups). CONCLUSION: Although the treatment success rate was higher in patients treated with surgery and fluoroquinolones compared to other groups, an additional significant benefit from surgery could not be demonstrated. Larger scale studies are needed to clarify this issue.

Evaluation of anxiety levels during intracavitary brachytherapy applications in women with gynecological malignancies.

PURPOSE: To evaluate the anxiety levels of women treated for gynecological malignancies using intracavitary brachytherapy. METHODS: Anxiety levels prior to and after intracavitary brachytherapy application and factors influencing anxiety levels were evaluated. Women were evaluated for quality of life and psychological status before each brachytherapy application using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0-7 = normal, 8-10 = borderline, 11-21 = abnormal. Women were also questioned about other factors which could affect anxiety levels such as marital status, education level, number of pregnancies and prior surgical history. RESULTS: Between January 2003 and August 2004, 146 women with a median age of 56 years were evaluated (range: 27-80). Eighty-six women had cervix uteri carcinoma and 63 had endometrial carcinoma. Sixty-seven women were premenopausal and 85 women were postmenopausal. The median pregnancy number was three (range = 0-10). Eighty-nine women had at least three children. Sixty-seven women had had previous operations. One hundred and twenty-five women were married and 24 women were unmarried or widowed. Before treatment, the anxiety scores were scored as normal in 49 (32%), borderline in 41 (28%), and abnormal in 59 (40%). Anxiety levels were lower in 69 women during the last application as compared with the pretreatment levels (p = 0.00). Marital status and pregnancy number showed a significant correlation with anxiety scores (p = 0.04). Age, level of education or having had a previous operation showed no significant correlation with anxiety level. CONCLUSION: These results indicate that intracavitary brachytherapy is associated with anxiety. Women need to be given detailed information before the brachytherapy application to reduce anxiety. Additional studies are needed to determine it.

Side effects associated with the treatment of multidrug-resistant tuberculosis.

SETTING: Süreyyapasa Centre for Chest Diseases and Thoracic Surgery, Istanbul, Turkey. OBJECTIVE: To report the frequency of treatment side effects in cases of multidrug-resistant (MDR-TB) tuberculosis. DESIGN: A retrospective review of the medical records of 263 patients who received individualised treatment for MDR-TB between April 1992 and June 2004. RESULTS: One or more side effects developed in 182 cases (69.2%). These effects led the clinicians to withdraw one or more drugs from the treatment regimen in 146 cases (55.5%). Side effects observed most frequently included: ototoxicity (41.8%), psychiatric disorders (21.3%), gastrointestinal disturbance (14.0%), arthralgia (11.4%), epileptic seizures (9.9%), hepatitis (4.5%), and dermatological effects (4.5%). At the time of analysis, treatment was successful in 204 (77.6%) cases. Fifty-nine patients (22.4%) had poor outcomes. CONCLUSION: Timely and aggressive management of drug side effects means that high side effect rates in MDR-TB treatment need not compromise success rates.