Impact of COVID-19 on patient-doctor interaction in a complex radiation therapy facility.

PURPOSE: In the last months, Italy faced a COVID-19 emergency and implemented preventive measures in order to protect patients and healthcare providers from a disease outbreak. The pandemic control strategies impacted patient experience directly. Questionnaires evaluating patients reported measures (PREMs) may assess critical issues and represent a helpful tool to measure the patient perception of healthcare service. Our aim was to prospectively assess patient satisfaction about doctor-patient interaction in a high-volume radiation therapy and oncology center during the COVID-19 pandemic. METHODS: Cancer patients receiving either systemic and/or radiation treatment underwent a survey. Two validated questionnaires (EORTC QLQ-C30, FACIT-TS-G version 1) and 14 specific questions evaluating patients' perception of COVID-19 measures were administered. RESULTS: One hundred twenty-five patients admitted to our department from 1-30 April 2020 completed the questionnaires. The majority (66.4%) of patients were women and the most common disease was breast cancer (40%). The average Global Health Status (GHS) of EORTC QLQ-C30 was 61.67. Emotional functioning, social, and cognitive domains obtained scores of 75.48, 80.13, and 84.67, respectively. FACIT-TS-G results revealed 120 patients rated the treatments effective and 108 patients thought the side effects were the same as expected or better. Most (89.6%) rated their treatment good, very good, or excellent. Concerning COVID-19-related questions, patients reported overall very good level of information. CONCLUSIONS: Despite the introduction of strict COVID-19 control measures, there was a high level of cancer outpatient satisfaction. The satisfaction levels may influence compliance, continuity of treatments, and patient-doctor communication, impacting the quality of clinical care in the next phases of the pandemic.

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer.

AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. CONCLUSION: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.

Hypothyroidism and hyponatremia: data from a series of patients with iatrogenic acute hypothyroidism undergoing radioactive iodine therapy after total thyroidectomy for thyroid cancer.

PURPOSE: The aim of the present study was to evaluate the role of hypothyroidism as a cause of hyponatremia in a clinical model of iatrogenic acute hypothyroidism due to thyroid hormone withdrawal prior to ablative radioactive iodine (RAI) therapy after total thyroidectomy. METHODS: The study group consisted of 101 differentiated thyroid cancer (DTC) patients (77 women and 24 men). Plasma concentration of thyroid-stimulating hormone ([TSH]) and sodium ([Na+]) was evaluated before total thyroidectomy (pre[TSH] and pre[Na+]) and on the day of RAI therapy (post[TSH] and post[Na+]). RESULTS: The frequency of hypothyroidism-associated hyponatremia was 4 % (4/101). Pre[Na+] was significantly higher than post[Na+] (140.7 ± 1.6 vs 138.7 ± 2.3 mEq/L, p = 0.012). Moreover, a linear correlation was identified between pre[Na+] and post[Na+]. CONCLUSIONS: Iatrogenic acute hypothyroidism-related hyponatremia is uncommon. However, because of the significant reduction of [Na+] in the transition from euthyroidism to iatrogenic hypothyroidism, the value of pre[Na+] should be viewed as a parameter to be considered. Since it acts as an independent risk factor for the development of hyponatremia, patients with a pre[Na+] close to the lower limit of normal range may deserve a closer monitoring of [Na+].

CyberKnife stereotactic radiotherapy for isolated recurrence in the prostatic bed.

PURPOSE: To report a clinical experience of stereotactic body radiation therapy (SBRT) for isolated recurrence in the prostatic bed from prostate cancer. MATERIALS AND METHODS: Between November 2011 and November 2013, 16 patients were treated with SBRT for a macroscopic isolated recurrence of prostate cancer in the prostatic bed. All patients were initially treated with radical prostatectomy, and half of them also received radiotherapy. Two schedules of SBRT were used: 30 Gy in 5 fractions in previously irradiated patients, 35 Gy in five fractions in radiotherapy-naïve patients. RESULTS: At a median follow-up of 10 months (range 2-21 months), a significant biochemical response was found in all but one patient. At imaging evaluation, no local progression was noted: 10 patients showed partial response while four stable disease. At the moment of analysis, all 16 patients were alive. Seven of them experienced distant relapse, while nine maintained biochemical control, with no further therapy. Median time to relapse was 9.3 months (range 3-15.2 months). The treatment was well tolerated: One patient experienced G2 acute genitourinary and gastrointestinal toxicity. CONCLUSIONS: Our experience shows that SBRT with CyberKnife for isolated nodal relapse is a safe and well-tolerated treatment.

Cyberknife treatment for low and intermediate risk prostate cancer.

Cyberknife is an emerging treatment for early stage prostate cancer. Between October 2012 and January 2014, 32 patients were treated in our institution. Prescribed dose was 35-36.25 Gy in five fractions. Biochemical response was observed in 22 patients. Four patients experienced G2 acute genitourinary toxicity and in two cases we recorded G3 acute GU toxicity. 5 patients experienced G2 acute proctitis. At last follow up visit, all patients were still alive. 29 remained free of disease at last follow up appointment, while three developed a biochemical recurrence. Our experience confirms the efficacy and safety of Cyberknife for localized prostate cancer.

Stereotactic radiotherapy for isolated nodal recurrence of prostate cancer.

PURPOSE: To report a clinical experience in stereotactic body radiation therapy (SBRT) for isolated nodal metastases from prostate cancer. MATERIALS AND METHODS: Between November 2011 and December 2013, 30 patients (39 lesions) were treated with SBRT, delivered using Cyberknife, for recurrent prostate cancer with isolated nodal metastases. Prescribed doses and schedules of fractionation varied, ranging from 24 Gy in 1 fraction to 36 Gy in 3 fractions. Most commonly used schedules were 30 Gy in 3 fractions and 36 in Gy in 3 fractions on alternating days. Biochemical response, acute and late toxicity were analyzed. RESULTS: At a median follow-up of 12 months (range 2-24.9), a significant reduction of PSA was observed in 24 cases, while PSA was stable in 1 case and raised in 9 cases. At the time of analysis, among the 30 patients treated, two were dead for systemic disease; 12 patients experienced a relapse of disease in other sites. Sixteen patients were still free of disease. In 24 cases, imaging evaluation 3 months after treatment was available. No in-field recurrence was detected. SBRT was well tolerated: One patient experienced G2 acute genitourinary toxicity. Late toxicity was evaluated in patients with more than 6 months of follow-up, and only one complained G1 proctitis. We did not observe any acute or late severe toxicity (≥G3). CONCLUSIONS: Our experience shows that SBRT for isolated nodal relapse from prostate cancer is a safe treatment, with promising results in terms of efficacy.

Hypofractionation in prostate cancer: radiobiological basis and clinical appliance.

External beam radiation therapy with conventional fractionation to a total dose of 76-80 Gy represents the most adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α / ß . Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting.

Treatment of invasive male breast cancer: a 40-year single-institution experience.

PURPOSE: We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. MATERIALS AND METHODS: We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. RESULTS: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). CONCLUSIONS: In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part I: Evolving technical choices and survival.

PURPOSE: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability. RESULTS: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS. CONCLUSIONS: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part II: Evolving technical choices and toxicity patterns.

PURPOSE: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared. RESULTS: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications. CONCLUSIONS: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.

Concomitant adjuvant chemo-radiation therapy with anthracycline-based regimens in breast cancer: a single centre experience.

PURPOSE: This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach. MATERIALS AND METHODS: From September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). RESULTS: Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients. CONCLUSIONS: In our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.

Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery.

AIMS: To evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery. MATERIALS AND METHODS: In total, 539 patients with pTis-pT1-pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons. RESULTS: At the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (+/- 0.5% standard error) and 2.1% (+/- 0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity. CONCLUSION: This type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis.

Use of tamoxifen in pT1a-pT1b, pN0 breast cancer.

PURPOSE: To evaluate if in low-risk breast cancer patients (pT1a-pT1b, pN0) tamoxifen can reduce local recurrence and improve survival. METHODS: Retrospectively 700 patients were analyzed. All patients were treated from 1980 to 2003 with conservative surgery plus radiotherapy at the University of Florence. No patients were treated with adjuvant chemotherapy. Tamoxifen was prescribed in 359 patients (51.3%). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. RESULTS: The univariate analysis for specific survival showed that only histological type and local recurrence were significant prognostic factors (log rank test: p=0.02 and p<0.0001, respectively). The Cox regression model by stepwise selection confirmed lobular histological type (p=0.008; HR: 3.83, 95% CI: 1.31-11.21) and local recurrence (p<0.001; HR: 9.05, 95% CI: 3.05-26.82) as independent prognostic factors for disease specific survival. For local disease free survival, multivariate analysis did not show any significant parameters. CONCLUSION: In our series tamoxifen did not seem to improve disease specific survival and local disease specific survival. The number of events in terms of death for cancer or in terms of local recurrence is too small in this group of patients. However, according to our results we suggest not to prescribe tamoxifen in patients affected by pT1a-pT1b, pN0 breast cancer.

The management of elderly patients with T1-T2 breast cancer treated with or without radiotherapy.

AIM: The aim of the current study is to identify a subgroup of patients with breast cancer who have a low risk of local recurrence after conservative surgery in order to avoid radiotherapy treatment. METHODS: A group of 472 patients underwent conservative surgery without radiotherapy, and it was compared to a second group of 755 patients with similar characteristics, but who had received radiotherapy treatment (RT) after conservative surgery. RESULTS: Breast relapse's univariate analysis demonstrated statistical significance for the following factors: radiotherapy treatment, clinical stage, pathological stage, positive axillary nodes and tumour grading. Different results were obtained studying breast relapse. In the no-RT group breast relapse was 10.6% while in the irradiated group it was 3.4%. The breast relapse incidence decreases as the age of the patients increases especially over 75 years of age. CONCLUSIONS: In conclusion, there is clinical evidence of avoiding adjuvant radiotherapy for patients over 75 years with T1-T2 cancer treated with quadrantectomy with a clear excision margin.

Tubular carcinoma of the breast: outcome and loco-regional recurrence in 307 patients.

PURPOSE: The aim of this study is to describe the University of Florence experience in evaluating clinical, pathologic and treatment factors as they are related to the outcome and loco-regional recurrence in patients with tubular breast carcinoma. MATERIAL AND METHODS: Three hundred and seven patients (median age 56.4 years, range 26-91 years) with histological verified tubular carcinoma of the breast were consecutively treated at University of Florence from 1976 to 2001. All patients were followed for a median of 8.4 years (range 3 months to 20 years). Thirty-seven women underwent mastectomy and 270 underwent breast conserving surgery. Positive axillary nodes were found in 15% of patients. Fifty-two patients did not undergo radiotherapy to whole breast after having breast conserving surgery. Tamoxifen was prescribed in 108 patients and chemotherapy in 21 patients, 15 out of 21 had positive axillary nodes. RESULTS: Cause specific survival was 99.6, 99.2 and 97.2% at 3, 5 and 10 years. Local recurrence rate was 1.9, 3.6 and 4.7% at 3, 5 and 10 years. Univariate statistical analysis was significant for specific survival and local recurrence for angiolymphatic invasion only (p=0.0004). CONCLUSIONS: In the absence of axillary disease and angiolymphatic invasion, conserving surgery with adjuvant radiotherapy is effective treatment of disease.

Uterine sarcoma: twenty-seven years of experience.

PURPOSE: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. PATIENTS AND METHODS: One hundred forty-one patients (median age: 56 years, range: 19-85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed müllerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. RESULTS: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p = 0.02), grade (p = 0.003), stage (p = 0.007), and age (p = 0.02). Multivariate analysis demonstrated significant prognostic values for stage (p = 0.02) and histology (p = 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant (p = 0.001) in reducing local recurrence. CONCLUSIONS: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy.