P. Foro

Five-year outcomes, cosmesis, and toxicity with 3-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation.

PURPOSE To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). METHODS AND MATERIALS 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. RESULTS The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. CONCLUSIONS APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI.

Predictors of Acute Esophagitis in Lung Cancer Patients Treated With Concurrent Three-Dimensional Conformal Radiotherapy and Chemotherapy

PURPOSE To evaluate the risk factors for acute esophagitis (AET) in lung cancer patients treated with concurrent 3D-CRT and chemotherapy. METHODS AND MATERIALS Data from 100 patients treated with concurrent chemoradiotherapy with a mean dose of 62.05 +/- 4.64 Gy were prospectively evaluated. Esophageal toxicity was graded according to criteria of the Radiation Therapy Oncology Group. The following dosimetric parameters were analyzed: length and volume of esophagus in treatment field, percentage of esophagus volume treated to >or=10, >or=20, >or=30, >or=35, >or=40, >or=45, >or=50, >or=55, and >or=60 Gy, and the maximum (D(max)) and mean doses (D(mean)) delivered to the esophagus. Also, we developed an esophagitis index (EI) to account the esophagitis grades over treatment time. RESULTS A total of 59 patients developed AET (Grade 1, 26 patients; Grade 2, 29 patients; and Grade 3, 4 patients). V50 was associated with AET duration (p = 0.017), AET Grade 1 duration (p = 0.016), maximum analgesia (p = 0.019), esophagitis index score (p = 0.024), and AET Grade >or=1 (p = 0.058). If V50 is <30% there is a 47.3% risk of AET Grade >or=1, which increases to 73.3% if V50 is >or=30% (p = 0.008). The predictive abilities of models (sensitivity and specificity) were calculated by receiver operating characeristic curves. CONCLUSIONS According to the receiver operating characeristic curve analysis, the 30% of esophageal volume receiving >or=50 Gy was the most statistically significant factor associated with AET Grade >or=1 and maximum analgesia (A(max)). There was an association with AET Grade >or=2 but it did not achieve statistical significance (p = 0.076).

Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

PURPOSE To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. METHODS AND MATERIALS 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. RESULTS The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). CONCLUSIONS In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.

PHASE II STUDY OF VINORELBINE AND ESTRAMUSTINE IN COMBINATION WITH CONFORMATIONAL RADIOTHERAPY FOR PATIENTS WITH HIGH-RISK PROSTATE CANCER

PURPOSE To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. METHODS AND MATERIALS Fifty patients received estramustine, 600 mg/m(2) daily, and vinorelbine, 25 mg/m(2), on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. RESULTS All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patients decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. CONCLUSIONS Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.

Long-term results and prognostic factors of patients with cervical carcinoma treated with concurrent chemoradiotherapy

Aims and backgroundTo evaluate the predictive factors of recurrence in cervical cancer treated with radical radiochemotherapy.MethodsA retrospective analysis of 56 women was performed. Response was assessed using the RECIST response. Overall survival and disease-free survival curves were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to analyse predictors of recurrence.ResultsLocal recurrence was documented in 16 patients and distant metastases in 15. The Kaplan-Meier survival probabilities were 95.1±6.4% at 3 years and 80.4±13.1% at 5 years and the Kaplan-Meier curve values for disease-free survival were 60.3±14.3% at 3 years and 53.0±15.7% at 5 years. Thirty-five patients were alive and 21 patients died, 19 from metastatic disease and 2 from other causes. Complete response after chemoradiation therapy, squamous cell carcinoma and tumour size ≤4 cm were significantly associated with outcome. In the Cox regression model, tumour size >4 cm (hazard ratio 7.48; 95% CI 2.71–20.6; p<0.001) and partial response (hazard ratio 7.09; 95% CI 2.82–17.8; p<0.001) were predictive factors for disease-free survival and partial response (hazard ratio 3.7; 95% CI 1.3–10.1; p<0.001) and non-squamous cell carcinoma (hazard ratio 3.5; 95% CI 1.2–9.7; p<0.001) were predictive factors for overall survival.ConclusionsNon-squamous histology and partial response were independent prognostic factors for overall survival and tumour size and partial response were independent prognostic variables for 5-year disease survival.

Impact of PSA implementation and combined radiation and hormonal therapy (RT + HT) on outcome of prostate cancer patients

Advances in the diagnosis and management of prostate cancer have been associated with changes in clinico-epidemiological characteristics and cancer-specific mortality. Secular trends of prostate cancer patients and its correlation with PSA implementation and the introduction of combined radiation and hormonal therapy (RT+HT) were assessed in a cohort of 910 cancer patients with histologically confirmed prostate cancer diagnosed between 1992 and 2005, and included in a hospital-based database. Relative survival before and after 1999 (when RT+HT for locally advanced disease was introduced) was compared. The mean age at diagnosis decreased from 72.9 years in 1992-1996 to 68.7 in 2003-2005 and the median PSA from 34 to 8 ng/ml. In patients with stages II and III, there was an increase in the indication of RT with or without HT and a decrease in the indication of surgery (from 87.5% to 44.2%). The overall relative 5-year survival increased from 67.3% (95% CI 60.2-75.2) to 92.9% (95% CI 87.3-98.9). The same trend in stage II and stage III cancer patients was found. There was an increase in survival coincidentally with a shift towards lower stages and PSA levels at presentation. Besides other factors, changes in death rates since 1999 could be explained by secular variations in the treatment of the disease, particularly the implementation of RT+HT in intermediate and high-risk locally advanced prostate cancer.

Once-Weekly Hypofractionated Radiotherapy for Breast Cancer in Elderly Patients: Efficacy and Tolerance in 486 Patients

Purpose Radiation therapy is a key treatment of breast cancer. Elderly patients with associated diseases that modify their performance status do not tolerate long periods of daily irradiation. The objective of this study is to analyze the results of weekly hypofractionated treatment in these patients. Material and Methods Between 1992 and 2016, we included 486 elderly patients presenting concomitant pathology or sociofamilial problems in which it was not feasible to propose conventional treatment. They were treated with conservative surgery or mastectomy and then adjuvant hypofractionated irradiation, administering 5 Gy or 6.25 Gy in 6 fractions, once a week (total dose 30–37.5 Gy) over 6 weeks. Results Breast cancer overall survival according to the Kaplan-Meier method at 5 years was 74.2% ± 2.3%; breast cancer disease-free survival was 90% ± 1.6%; local relapse-free survival was 96.5% ± 1% showing that patients die more from other causes and not from their neoplasia. Acute dermatitis was mild (75.6% of the patients grades I–III) and 30.6% had moderate chronic fibrosis. Conclusions The once-weekly hypofractionated radiotherapy is a feasible and convenient option for elderly patients with breast cancer. It is a safe treatment modality with similar survival and local control results compared to standard fractionation, while the side effects are acceptable.

EP-1221: Accelerated hypofractionated three-dimensional conformal radiation therapy (AHRT) for NSCLC

Results: The main result was the reduction in primary and nodal volumes due to better definition of lung mass and nearby lung Collapse , the latter could be easily defined in 14 cases on the DW-MRI vs. 7 cases only by CT scans (P=0.016). Median GTV total (sum of 1ry and nodal GTV), on MRI Diffusion compared to that on the CT scan was 354 and 386 cm3 respectively (P= 0.009). In 15 cases, a mean decrease in the GTV total of 34% ±56% (median, 9%; range, 0.232.5%) by using DW-MRI. only in three other cases a mean increase in the GTV total of 12.7% ±14.9% (median, 9.7%; range, 0.4221%). was found. The median PTVs on the CT scans vs. the MRI Diffusion were 1623 (range, 493–2965 cm3) & 1419 (range, 542–3158 cm3) respectively which was statistically non significant (P= 0.391).

Conservative treatment in noninvasive breast cancer

Background The elective treatment for noninvasive breast carcinoma has not yet been established. As a result of mammographic screening programs, the incidence of noninvasive tumors has increased and has lead to the same controversy already present had with invasive carcinomas: mastectomy or conserving therapy. Methods Since 1990, 101 patients with noninvasive breast cancer were treated with irradiation following breast-conserving surgery. All the patients had irradiation of the whole breast (mean dose, 47.6 ± 1.2 Gy). The radiation dose boost to the tumor bed was delivered in 28.7% of the cases (mean dose, 21.03 ± 3.06 Gy), and in 71.3%, the boost was not administered. Results With a median follow-up of 34 months, survival is 100%. The disease-free survival at 5 years by the Kaplan-Meier method is 93.6 ± 8.65. Conclusions The conserving treatment is a valid option for treatment of patients with ductal carcinoma in situ.