Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Computed Tomography Perfusion of Prostate Cancer: Diagnostic Value of Quantitative Analysis.

OBJECTIVE: The aim of the study was to assess the diagnostic value of computed tomography perfusion (CTp) of prostate in distinguishing between normal tissue and malignant lesion by using quantitative threshold values of CTp parameters. MATERIALS AND METHODS: Sixty-one consecutive men with indication for radical prostatectomy were prospectively enrolled. All patients were intravenously injected with 80-mL bolus of nonionic iodinated contrast medium during cine-mode acquisition protocol. Perfusion data sets were analyzed by a dedicated software system and values for each of the 4 CTp parameters (blood volume, blood flow, mean transit time, and permeability surface-area product measurements) were recorded. Receiver operating characteristic curves were calculated to find which CTp parameter and which cutoff value might reveal the best diagnostic accuracy. Histopathology was used as reference standard. RESULTS: Statistical correlation between radiological and pathological results was performed on 48 patients using 3456 segmented squares. Blood volume and permeability surface revealed the best diagnostic accuracy for differentiating between malignant and benign squares, with cutoff values of 6.1 and 16.5, respectively, and a sensitivity of 84.8% and 81.8%, respectively. All parameters showed also a high negative predictive value: 97.1% for blood volume and 95.4% for permeability surface. CONCLUSIONS: Blood volume and permeability surface are the 2 CTp parameters with the highest diagnostic accuracy in differentiating between normal tissue and prostatic neoplasia. Due to the extremely high negative predictive value, they are particularly valuable in excluding the presence of cancer and thus resulting potentially useful in assessing cancer response to adjuvant therapy.

Modeling the risk of radiation-induced lung fibrosis: Irradiated heart tissue is as important as irradiated lung.

PURPOSE: We used normal tissue complication probability (NTCP) modeling to explore the impact of heart irradiation on radiation-induced lung fibrosis (RILF). MATERIALS AND METHODS: We retrospectively reviewed for RILF 148 consecutive Hodgkin lymphoma (HL) patients treated with sequential chemo-radiotherapy (CHT-RT). Left, right, total lung and heart dose-volume and dose-mass parameters along with clinical, disease and treatment-related characteristics were analyzed. NTCP modeling by multivariate logistic regression analysis using bootstrapping was performed. Models were evaluated by Spearman Rs coefficient and ROC area. RESULTS: At a median time of 13months, 18 out of 115 analyzable patients (15.6%) developed RILF after treatment. A three-variable predictive model resulted to be optimal for RILF. The two models most frequently selected by bootstrap included increasing age and mass of heart receiving >30Gy as common predictors, in combination with left lung V5 (Rs=0.35, AUC=0.78), or alternatively, the lungs near maximum dose D2% (Rs=0.38, AUC=0.80). CONCLUSION: CHT-RT may cause lung injury in a small, but significant fraction of HL patients. Our results suggest that aging along with both heart and lung irradiation plays a fundamental role in the risk of developing RILF.

Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer.

PURPOSE: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy. MATERIALS AND METHODS: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25-2.28 Gy each administered in 6 weeks up to a total dose of 67.5-68.4 Gy (range, 64.5-71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation. RESULTS: With a median follow up of 27 months (range 6-40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity. CONCLUSION: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time.

SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation.

BACKGROUND: The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI) after BCS (breast conserving surgery). METHODS: A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms) in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis. RESULTS: A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val) (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047). CONCLUSIONS: The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01316328.

Dose escalation for prostate cancer using the three-dimensional conformal dynamic arc technique: analysis of 542 consecutive patients.

PURPOSE: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. METHODS AND MATERIALS: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. RESULTS: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed (p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. CONCLUSIONS: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

Three-dimensional conformal or stereotactic reirradiation of recurrent, metastatic or new primary tumors. Analysis of 108 patients.

PURPOSE: To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques. PATIENTS AND METHODS: 108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy. RESULTS: Median follow-up was 7 months (range, 1-50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent. CONCLUSION: A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.

Transabdominal ultrasonography, computed tomography and electronic portal imaging for 3-dimensional conformal radiotherapy for prostate cancer.

PURPOSE: To evaluate the feasibility and accuracy of daily B-mode acquisition and targeting ultrasound-based prostate localization (BAT) and to compare it with computed tomography (CT) and electronic portal imaging (EPI) in 3-dimensional conformal radiotherapy (3-D CRT) for prostate cancer. PATIENTS AND METHODS: Ten patients were treated with 3-D CRT (72 Gy/30 fractions, 2.4 Gy/fraction, equivalent to 80 Gy/40 fractions, for alpha/beta ratio of 1.5 Gy) and daily BAT-based prostate localization. For the first 5 fractions, CT and EPI were also performed in order to compare organ-motion and set-up error, respectively. RESULTS: 287 BAT-, 50 CT- and 46 EPI-alignments were performed. The average BAT-determined misalignments in latero-lateral, antero-posterior and cranio-caudal directions were -0.9 mm+/-3.3 mm, 1.0 mm+/-4.0 mm and -0.9 mm+/-3.8 mm, respectively. The differences between BAT- and CT-determined organ-motion in latero-lateral, antero-posterior and cranio-caudal directions were 2.7 mm+/-1.9 mm, 3.9+/-2.8 mm and 3.4 +/- 3.0 mm, respectively. Weak correlation was found between BAT- and CT-determined misalignments in antero-posterior direction, while no correlation was observed in latero-lateral and cranio-caudal directions. The correlation was more significant when only data of good image-quality patients were analyzed (8 patients). CONCLUSION: BAT ensures the relative positions of target are the same during treatment and in treatment plan, however, the reliability of alignment is patient-dependent. The average BAT-determined misalignments were small, confirming the prevalence of random errors in 3-D CRT. Further study is warranted in order to establish the clinical value of BAT.

Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: a retrospective analysis of seventy-three patients.

PURPOSE: To evaluate the incidence of thyroid disorders and dose distribution to the thyroid in patients treated with radiotherapy for head-and-neck carcinomas. METHODS AND MATERIALS: A retrospective evaluation of data from 73 patients treated for head-and-neck cancers in our department was performed. Thyroid function was evaluated mainly by the measurement of thyrotropin (thyroid stimulating hormone [TSH]). A retrospective analysis of treatment plans was performed for 57 patients. Percentages of thyroid glandular volume absorbing 10, 30, and 50 Gy (V10, V30, and V50 respectively) were considered for statistical analysis. RESULTS: A majority of patients (61%) had a normal thyroid function whereas 19 patients (26%) had hypothyroidism. Mean thyroid volume was 30.39 cc. Point 3 (located at isthmus) absorbed lower doses compared with other points (p < 0.0001). Median values of V10, V30, and V50 were 92% (range, 57-100%), 75% (range, 28.5-100%), and 35% (range, 3-83%) respectively. Gender was associated with toxicity (presence of any kind of thyroid disorders) (p < 0.05), with females displaying higher levels of TSHr (relative TSH = patient's value/maximum value of the laboratory range) (p = 0.0005) and smaller thyroid volume (p = 0.0012) compared with male population. TSHr values were associated with thyroid volume, and the presence of midline shielding block in the anterior field was associated with relative free thyroxine (FT4r = patient's value/maximum value of the laboratory range) values. CONCLUSIONS: Gender and thyroid volume seem to play an important role in the occurrence of thyroid toxicity, but further studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are needed.