Contouring workload in adjuvant breast cancer radiotherapy.

PURPOSE: To measure the impact of contouring on worktime in the adjuvant radiation treatment of breast cancer, and to identify factors that might affect the measurements. MATERIAL AND METHODS: The dates and times of contouring clinical target volumes and organs at risk were recorded by a senior and by two junior radiation oncologists. Outcome measurements were contour times and the time from start to approval. The factors evaluated were patient age, type of surgery, radiation targets and setup, operator, planning station, part of the day and day of the week on which the contouring started. The Welch test was used to comparatively assess the measurements. RESULTS: Two hundred and three cases were included in the analysis. The mean contour time per patient was 34minutes for a mean of 4.72 structures, with a mean of 7.1minutes per structure. The clinical target volume and organs at risk times did not differ significantly. The mean time from start to approval per patient was 29.4hours. Factors significantly associated with longer contour times were breast-conserving surgery (P=0.026), prone setup (P=0.002), junior operator (P<0.0001), Pinnacle planning station (P=0.026), contouring start in the morning (P=0.001), and contouring start by the end of the week (P<0.0001). Factors significantly associated with time from start to approval were age (P=0.038), junior operator (P<0.0001), planning station (P=0.016), and contouring start by the end of the week (P=0.004). CONCLUSION: Contouring is a time-consuming process. Each delineated structure influences worktime, and many factors may be targeted for optimization of the workflow. These preliminary data will serve as basis for future prospective studies to determine how to establish a cost-effective solution.

Evaluation of acute skin toxicity of breast radiotherapy using thermography: Results of a prospective single-centre trial.

PURPOSE: Radiotherapy is a common adjuvant treatment of breast cancer. Acute radiation-induced dermatitis is a frequent side effect. We hypothesized whether it is possible to capture the increase of local temperature as a surrogate of the inflammatory state induced by radiotherapy. We designed a prospective, observational, single-centre study to acquire data on temperature rise in the treated breast during the course of radiotherapy, establish a possible association with the occurrence of dermatitis and investigate the predictive value of temperature increase in future occurrences of radiation-induced dermatitis. PATIENTS AND METHODS: All patients presenting for neoadjuvant or adjuvant radiotherapy during the course of breast cancer treatment at the university hospital of Martinique were considered for inclusion. Every week, patients were examined by two trained investigators for the occurrence of radiation-induced dermatitis, graded based on Radiotherapy Oncology Group, Common Terminology Criteria for Adverse Events v.4.0 and Wright scales. A frontal thermal image of torso was taken in strictly controlled conditions, with a calibrated TE-Q1 camera (Thermal Expert, i3systems, Daejeon, Korea). We studied temperature differences between the irradiated breast or thoracic wall and the contralateral area. For each thermal picture, we measured the difference in maximum temperature as well as the difference in minimum temperature and the difference in the average temperature in the considered area. We studied the evolution of these parameters over time week after week, measuring the maximum recorded difference and its correlation to acute radiation dermatitis intensity. RESULTS: Sixty-four consecutive patients were included. For all patients, we noticed an increase of temperature during the course of radiotherapy. Difference in maximum, minimum and average temperature was higher between the two breasts of patients with a radiation-induced dermatitis grade 2 or above compared to patients with no or mild dermatitis. Higher temperatures were also significantly associated with an increased sensation of discomfort, as recorded by questionnaire (P<0.05). CONCLUSION: As expected from the inflammatory phenomena involved in radiation-induced dermatitis, a noticeable increase in temperature during the course of radiotherapy was seen in all patients. Furthermore, high-grade radiation-induced dermatitis was strongly associated with an additional increase in local temperature, which is probably linked to the intense inflammatory reaction. Lastly, with a 1.4°C threshold set beforehand, it is possible to anticipate the occurrence of radiation-induced dermatitis, with interesting positive and negative predictive values of 70% and 77%, respectively in our population. We note that these results need to be confirmed in a dedicated study.

Curative brachytherapy for prostate cancer in African-Caribbean patients: A retrospective analysis of 370 consecutive cases.

PURPOSE: Prostate cancer is the most frequent malignancy in African-Caribbean men, a population sharing common genetic traits with African-American (AA) but presenting also genomic and epidemiologic specificities. Despite socioeconomic disparities with French mainland, all patients were treated within the French state-financed equal-access health care system. In this study, we report biochemical outcomes of patients treated by brachytherapy in our department from 2005 to 2014 in an African-Caribbean population. METHODS AND MATERIALS: Three hundred seventy consecutive patients receiving 125I brachytherapy as a curative treatment for early-stage (localized) disease between 2005 and 2014 were recorded. Selected patients presented with low-risk disease: initial prostate-specific antigen (PSA) <10 ng/mL, clinical stage ≤ T2c, and Gleason score <7. Patients with intermediate risk of recurrence were also included on a case-to-case basis with prostate-specific antigen <15 or Gleason score 7 (3 + 4). Biochemical failure free-survival was defined according to the American Society for Radiation Oncology nadir+2 definition. RESULTS: The 3-year and 5-year biochemical failure free-survival for the entire cohort were 98.3% and 91.6%, respectively. For patients with low- and intermediate-risk disease, the 5-year BBFS rates were 92.1% and 90.8%, respectively. In univariate and multivariate analyses, only Gleason score (<7 vs. 7; p =  0.030 vs. p < 0.05) was a significant predictor of biochemical failure. The overall rate of late and acute Grade 2 or higher genitourinary toxicity was 12.6% and 10.3%. CONCLUSIONS: In this large single-center series, brachytherapy achieved excellent rates of medium-term biochemical control in both low and selected intermediate-risk localized prostate cancer in African-Caribbean patients. Brachytherapy seems to be an excellent choice of treatment, with excellent outcomes and limited morbidity for African-Caribbean populations.

Prostate-specific antigen bounce after curative brachytherapy for early-stage prostate cancer: A study of 274 African-Caribbean patients.

BACKGROUND: Prostate cancer incidence in the African-Caribbean population ranks among the highest worldwide. We aim to evaluate the prostate-specific antigen (PSA) kinetics after brachytherapy, which so far remains unknown in this population. METHODS AND MATERIALS: From 2005 to 2013, 371 patients received (125)I brachytherapy of 145 Gy for early-stage prostate cancer. Eligibility criteria were cTNM ≤T2c, Gleason score ≤7, and initial PSA ≤15 ng/mL. Pretreatment androgen deprivation therapy was allowed. PSA bounce was defined as an increase of ≥0.4 ng/mL, lasting ≥6 months, followed by a decrease without any anticancer therapy. We examined PSA kinetics during followup. RESULTS: For the 274 patients with at least 24 months followup, median age was 62 years old (range, 45-76). Initial PSA was <10 ng/mL in 244 and 10-15 ng/mL in 30 patients; 40 received androgen deprivation therapy. With a median followup of 50 months (range, 24-125), PSA declined continuously in 168 (61%) patients, bounced in 87 (31%), and initially declined and then rose in 22 (8%) patients. Among these latter patients, 18 presented clinical recurrence. Mean bounce intensity was 2.0 ng/mL (median, 1.2; range, 0.4-12.4). Bounces occurred in average 12 months after brachytherapy. Patients with bounce were significantly younger: mean age 59 vs. 63 years old in patients without bounce, p <0.001. Bounce was also significantly associated with the immediate post-brachytherapy PSA, mean 4.0 among bounce cases vs. 2.9 among non-bounce cases, p < 0.001. Bounce was not associated with recurrence. CONCLUSIONS: PSA bounce in our African-Caribbean population seemed earlier and was more intense than described in other populations. Early increase of PSA should not be ascribed to treatment failure.

Impact of intensity-modulated and image-guided radiotherapy on elderly patients undergoing chemoradiation for locally advanced head and neck cancer.

PURPOSE: In this work, the treatment tolerance of elderly patients (≥70 years) undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed. PATIENTS AND METHODS: A retrospective review of 112 patients undergoing concurrent chemoradiation for locally advanced head and neck cancer was performed. Treatment toxicity, protocol violations, long-term complications, and survival were compared between 85 younger patients (< 70 years) and 27 older patients (≥ 70 years). RESULTS: Grade 3-4 treatment toxicity was observed in 88.2% and 88.8% for younger and older patients, respectively. Mean weight loss and treatment break were 5.9 and 3.9 kg (p = 0.03) and 7.3 and 7.8 days (p = 0.8) for younger and older patients, respectively. Seven patients (8.2%) did not complete treatment in the younger group compared to 1 patient (3.7%) in the older group (p = 0.6). No significant differences in protocol violations and survival were found between the two groups. CONCLUSION: Compared to younger patients, elderly patients with locally advanced head and neck cancer tolerated chemoradiation with IMRT and IGRT well, and should not be denied curative treatment based solely on age.

Adenoid cystic carcinoma of the Bartholin's gland: case report and systematic review of the literature.

Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare malignancy of the female genital tract. Seventy-nine cases have been reported in the literature. A 40-year-old women presented to our clinic with twice locally recurrent ACC of Bartholin's gland of the left vulva despite hemivulvectomy. Adjuvant radiotherapy was delivered after the third resection. There was no local recurrence after three years follow-up, although she developed lung metastases that remain under control with oral cyclophosphamide. Our case confirms the literature review, which indicates a slow growing tumor with frequent local recurrences (30%) and distant metastases (31%). Adjuvant radiotherapy and/or chemotherapy should be considered in the management of ACC of Bartholin's gland.

[Innovations in locoregional treatments of breast cancer]. / Innovations dans le traitement locorégional du cancer du sein.

Breast conserving therapy including breast conserving surgery followed by radiation therapy is the treatment of choice for early breast cancer. Sentinel lymph node biopsy is a minimally approach that allows to evaluate the axilla with less morbidity and avoid an axillary lymph node biopsy. This surgical technique is now evaluated in more specific situations. Modern surgical techniques such as oncoplastic surgery allow to excise larger tumors and obtain better cosmetic results. In a near future it is expected that intraoperative radiation therapy will remplace classicals approaches of radiotherapy for selected patients.

Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors.

BACKGROUND: Radiotherapy of the left breast is associated with higher cardiovascular mortality linked to cardiotoxic effect of irradiation. Radiotherapy of inner quadrants can be associated with greater heart irradiation, but no study has evaluated the effect of inner-quadrant irradiation on cardiovascular mortality. PATIENTS AND METHODS: We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis. RESULTS: After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1-5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors. CONCLUSIONS: Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotected.

Human papillomavirus-associated oropharyngeal cancer: a new clinical entity.

The incidence of oropharyngeal cancers is rising worldwide in both nonsmokers and nondrinkers. Epidemiology studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. Despite initial presentation with locally advanced disease and poorly differentiated histology, HPV-associated oropharyngeal carcinoma is associated with a good prognosis because its response to chemotherapy and radiation. Clinicians should be aware of the risk of oropharyngeal cancer in young people to avoid unnecessary delay in diagnosis and treatment. A history of oral sex should be elicited in young patients with enlarged neck nodes and/or tonsillar masses.

Impact of a positive family history on diagnosis, management, and survival of breast cancer: different effects across socio-economic groups.

BACKGROUND: This study aims to investigate whether increased awareness of breast cancer, due to a positive family history (FH), reduces diagnostic, therapeutic, and survival differences between women of low versus high socio-economic status (SES). METHODS: All breast cancer patients registered between 1990 and 2005 at the population-based Geneva Cancer Registry were included. With multivariate logistic and Cox regression analysis, we estimated the impact of SES and FH on method of detection, treatment, and mortality from breast cancer. RESULTS: SES discrepancies in method of detection and suboptimal treatment, as seen among women without a FH, disappeared in the presence of a positive FH. SES differences in stage and survival remained regardless of the presence of a positive FH. Overall, positive FH was associated with better survival. This effect was the strongest in women of high SES (age-adjusted Hazard Ratio [HR(ageadj)] 0.54 [0.3-1.0]) but less pronounced in women of middle (0.77 [0.6-1.0]), and absent in women of low SES (0.80 [0.5-1.2]). CONCLUSION: A positive FH of breast cancer may reduce SES differences in access to screening and optimal treatment. However, even with better access to early detection and optimal treatment, women of low SES have higher risks of death from their disease than those of high SES.

Hormonal therapy for oestrogen receptor-negative breast cancer is associated with higher disease-specific mortality.

BACKGROUND: Tamoxifen has a remarkable impact on the outcome of oestrogen receptor (ER)-positive breast cancer. Without proven benefits, tamoxifen is occasionally prescribed for women with ER-negative disease. This population-based study aims to estimate the impact of tamoxifen on the outcome of ER-negative disease. METHODS: We identified all women (n = 528) diagnosed with ER-negative invasive breast cancer between 1995 and 2005. With Cox regression analysis, we calculated breast cancer mortality risks of patients treated with tamoxifen compared with those treated without tamoxifen. We adjusted these risks for the individual probabilities (propensity scores) of having received tamoxifen. RESULTS: Sixty-nine patients (13%) with ER-negative disease were treated with tamoxifen. Five-year disease-specific survival for women treated with versus without tamoxifen were 62% [95% confidence interval (CI) 48% to 76%] and 79% (95% CI 75% to 83%), respectively (P(Log-rank) < 0.001). For ER-negative patients, risk of death from breast cancer was significantly increased in those treated with tamoxifen compared with patients treated without tamoxifen (adjusted hazard ratio = 1.7, 95% CI 1.1-2.9, P = 0.031). CONCLUSION: Our results show that patients with ER-negative breast cancer treated with tamoxifen have an increased risk of death from their disease. Tamoxifen use should be avoided for these patients.

Safety and effectiveness of vascular endoprosthesis for malignant superior vena cava syndrome.

BACKGROUND: Superior vena cava syndrome management has been traditionally radiation therapy, chemotherapy or chemoradiation, depending on the underlying malignancy involved and individual clinicopathological features of the case. Recent emergence of endovascular stents offer the opportunity for immediate relief of the venous stenosis. This review examines findings from the published series which used endovascular prosthesis for this syndrome with regards to efficacy and safety. METHODS: Literature search identified studies using endovascular stents as initial therapy or for recurrence of malignant superior vena cava syndrome. Effectiveness and toxicity from stent placement was assessed. RESULTS: Endovascular stent placement provides immediate haemodynamic relief of venous compression either before or after definitive therapy in the majority of cancer patients. Severe bleedings, cardiopulmonary complications and stent migrations remain significant problems for patient management. CONCLUSIONS: Endovascular prosthesis is an effective modality for malignant superior vena cava syndrome with acceptable morbidity. Prospective studies should be performed to determine the optimal anticoagulation regimen.

No nodal cutoff in node-positive breast cancer women treated with mastectomy.

PURPOSE: To search for a prognostic cutoff in the number of involved axillary lymph-nodes, in T1-T2 node-positive (N+) breast cancer treated with mastectomy without radiotherapy. MATERIALS AND METHODS: Women aged 51-64 years presenting with a first primary T1-T2, N+, M0 unilateral carcinoma diagnosed in 1988-97 were selected from the SEER 9-registries. Cutoffs from 1 to 23 nodes were scanned with Cox models that included diagnostic year, age, area, race, marital status, histology, grade, hormone receptors, tumor location, size, and nodes examined. Outcomes were breast cancer specific and any-cause death. RESULTS: The overall mortality hazard ratio of a higher number of involved nodes as compared with a lower number ranged from 1.78 [95% confidence 1.58-1.99] with 1-node cutoff, to 3.65 [2.52-5.29] with 23-nodes cutoff. Breast cancer specific mortality hazard ratio ranged from 1.99 [1.73-2.29] with 1-node cutoff, to 4.63 [3.11-6.91] with 23-nodes cutoff. The graph of the hazard ratios showed a continuously increasing risk of overall and breast cancer specific mortality, without any identifiable cutpoint change. CONCLUSION: The results show no prognostic cutoff in the number of involved axillary lymph nodes in patients who did not receive radiotherapy. The rationale of nodal cutoff as an indicator for post-mastectomy adjuvant treatment in node-positive patients should be questioned.

The effect of timing of the provision of information on anxiety and satisfaction of cancer patients receiving radiotherapy.

BACKGROUND: To improve the provision of information to their radiotherapy patients, the authors examined whether the timing of given written information has an effect on anxiety and satisfaction. METHODS: Two sources of information were used: 1) a booklet with a description of radiotherapy procedures and the sensations patients can experience; 2) teaching sheets with treatment-site-related information. 68 patients were randomized to a simultaneous-information group (n = 31) and a stepwise-information group (n = 37). The patients were being treated for cancers of the breast, lung, head, and neck or the pelvic region. The authors analyzed the impacts of several variables on patient learning, including anxiety, age, gender, support, referral, stage of illness, and diagnosis. Assessments were recorded before the simulation procedure and during the second and last weeks of treatment. RESULTS: The stepwise-information group was significantly less anxious before simulation (p = 0.02) and more satisfied (p = 0.001). Of the variables studied, only the support variable was associated with high state anxiety (p < 0.0001). CONCLUSIONS: Provision of patient information in a stepwise format leads to less treatment-related anxiety and greater patient satisfaction among radiation therapy patient undergoing simulation.

Characteristics and clinical application of a treatment simulator with Ct-option.

BACKGROUND AND PURPOSE: The integration of a scanner for computed tomography (CT) and a treatment simulator (Sim-CT, Elekta Oncology Systems, Crawley, UK) has been studied in a clinical situation. Image quality, hounsfield units (HU) and linearity have been evaluated as well as the implications for treatment planning. The additional dose to the patient has also been highlighted. MATERIAL AND METHODS: Image data is acquired using an array of solid state X-ray detectors attached externally to the simulator's image intensifier. Three different fields of view (FOV: 25.0 cm, 35.0 cm and 50.0 cm) with 0.2 cm, 0.5 cm and 1.0 cm slice thickness can be selected and the system allows for an aperture diameter of 92.0 cm at standard isocentric height. The CT performance has been characterized with several criteria: spatial resolution, contrast sensitivity, geometric accuracy, reliability of hounsfield units and the radiation output level. The spatial resolution gauge of the nuclear associates quality phantom (NAQP) as well as modulation transfer functions (MTF) have been applied to evaluate the spatial resolution. Contrast sensitivity and HU measurements have been performed by means of the NAQP and a HU conversion phantom that allows inserts with different electron densities. The computed tomography dose index (CTDI) of the CT-option has been monitored with a pencil shaped ionization chamber. Treatment planning and dose calculations for heterogeneity correction based on the Sim-CT images generated from an anthropomorphic phantom as well as from ten patients have been compared with similar treatment plans based on identical, yet diagnostic CT (DCT) images. RESULTS: The last row of holes that are resolved in the spatial resolution gauge of the NAQP are either 0.150 cm or 0.175 cm depending on the FOV and the applied reconstruction filter. These are consistent with the MTF curves showing cut-off frequencies ranging from 5.3 lp/cm to 7.1 lp/cm. Linear regression analysis of HU versus electron densities revealed a correlation coefficient of 0.99. Contrast, pixel size and geometric accuracy are within specifications. Computed tomography dose index values of 0.204 Gy/As and 0.069 Gy/As have been observed with dose measurements in the center of a 16 cm diameter and 32 cm diameter phantom, respectively for large FOV. Small FOV yields CTDI values of 0.925 Gy/As and 0.358 Gy/As which is a factor ten higher than the results obtained from a DCT under similar acquisition conditions. The phantom studies showed excellent agreement between dose distributions generated with the Sim-CT and DCT HU. The deviations between the calculated settings of monitor units as well as the maximum dose in three dimensions were less than 1% for the treatment plans based on either of these HU both for pelvic as well as thoracic simulations. The patient studies confirmed these results. CONCLUSIONS: The CT-option can be considered as an added value to the simulation process and the images acquired on the Sim-CT system are adequate for dose calculation with tissue heterogeneity correction. The good image quality, however, is compromised by the relative high dose values to the patient. The considerable load to the conventional X-ray tube currently limits the Sim-CT to seven image acquisitions per patient and therefore the system is limited in its capability to perform full three-dimensional reconstruction.

Use of a simulator with CT option in radiotherapy of macular degeneration.

PURPOSE: To assess the accuracy of a conventional simulation procedure in radiotherapy of age-related macular degeneration. METHODS AND MATERIALS: A computed tomographic (CT) extension attached to the treatment simulator was used to acquire CT images immediately after conventional simulation in 18 patients referred for treatment of age-related macular degeneration. Analysis was performed on 16 one-sided treatment cases for whom images were obtained. Error was estimated by the displacement between the observed treatment isocenter and the intended isocenter based on reconstructed eye geometry. RESULTS: Based on single slice measurements, the mean error amplitude was 2.3 mm (range 0.2-5.6). Based on three-dimensional eye globe reconstruction, the mean error amplitude was 2.8 mm (range 0.8-5.3). An incidental finding previously unreported was the lower image quality at the center of the simulator-CT image acquisition field. CONCLUSIONS: Small but significant errors from conventional simulation were noted. The integrated simulation-CT procedure may help correct the errors to improve the accuracy of simulation setup. The lower image quality at the center of image acquisition field requires adaptation of the simulation-CT procedure.

Power of test comparing independent proportions.

In clinical studies, trial size may be bounded by scarcity of resources and cannot be planned at will to attain some given power level as provided by sample size tables. In such a situation it may be useful to compute power consequent to the limited trial size. A procedure in BASIC is provided for approximate computation of power of a test comparing independent proportions when trial size is known to be limited.