Survival analysis and prognostic factors in posterior fossa ependymomas in children and adolescents.

OBJECTIVE: In this study, the authors aimed to analyze the overall survival (OS) and progression-free survival (PFS) of patients younger than 18 years of age who were diagnosed with posterior fossa ependymomas, and to identify prognostic factors such as the degree of resection, tumor topography, and involvement of the lesion in the hindbrain. METHODS: The authors performed a retrospective cohort study of patients younger than 18 years of age, treated beginning in 2000, with a diagnosis of posterior fossa ependymoma. Ependymomas were separated into three groups: tumors restricted to the fourth ventricle, tumors inside the fourth ventricle and exiting from the foramen of Luschka, and tumors inside the fourth ventricle and completely surrounding the hindbrain. Furthermore, the tumors were classified by molecular group using the staining method for H3K27me3. Statistical analysis was performed using Kaplan-Meier survival curves, with p < 0.05 considered statistically significant. RESULTS: Of 1693 patients who underwent surgical treatment between January 2000 and May 2021, 55 patients who met the inclusion criteria were included. The median age at diagnosis was 2.98 years. The median OS was 44 months, and the survival rates at 1, 5, and 10 years were 92.5%, 49.1%, and 38.3%, respectively. The cases were assigned to two posterior fossa ependymoma molecular groups: 35 (63.6%) cases to group A and 8 (14.5%) to group B. The median ages in groups A and B were 2.94 and 2.85 years and the median OS values were 44 and 38 months, respectively (p = 0.9245). Statistical analysis was performed on multiple variables, including age, sex, histological grade, Ki-67 expression, tumor volume, extent of resection, and adjuvant therapies. The median PFS of patients with dorsal-only involvement was 28 months; for dorsolateral involvement, it was 15 months; and for total involvement, it was 9.5 months (p = 0.0464). No statistically significant difference was found for OS. There was a statistically significant difference between the proportion of patients in whom gross-total resection was achieved in the dorsal-only involvement group (73.1%, 19/26) and those in the total involvement group (0%, 0/6) (p = 0.0019). CONCLUSIONS: This study confirmed that the extent of resection has an impact on OS and PFS. The authors found that adjuvant radiotherapy resulted in a higher OS but did not prevent progression, that the pattern of involvement of the brainstem in the tumor at diagnosis could elicit important information regarding the patient's prognosis regarding PFS, and that the total involvement of the rhombencephalon impaired the gross-total resection of these tumors.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Postmastectomy Radiation Therapy Bolus Associated Complications in Patients Who Underwent 2-stage Breast Reconstruction.

Purpose: This study aimed to evaluate the association of bolus and 2-stage breast reconstruction complications, and whether the dosimetric advantage translates into improvements in local control. Methods and Materials: We retrospectively analyzed data from 2008 to 2019 of women who underwent a mastectomy and a planned 2-stage breast reconstruction, followed by adjuvant radiation therapy. We reviewed all data from medical records and radiation plans regarding patient characteristics, diagnoses, surgeries, complications, pathology, staging, systemic therapy, radiation therapy, and outcomes, and compared complication rates according to bolus usage. Results: A total of 288 women, age 25 to 71 years, were included in the study. Of these women, 6 were treated with daily bolus and 19 with alternate days bolus, totaling 25 of 288 patients (8.7%) in the bolus group. A total of 226 patients (78.5%) had the second stage performed. The median follow-up time was 61 months. The rates for 5-year overall survival and locoregional control were both 97%, and the metastasis-free rate was 83%. In the first stage, 6.25% of patients in the entire cohort had an infection and 4.2% had implant loss. Daily bolus significantly increased the risk of expander infection (hazard ratio [HR]: 10.3; 95% confidence interval [CI], 1.7-61.8) and loss (HR: 13.89; 95% CI, 2.24-85.98), but alternate-day bolus showed a nonsignificant increase for expander infection (HR: 1.14; 95% CI, 0.14-9.295) and loss (HR: 1.5; 95% CI, 0.19-12.87). Bolus was not associated with second-stage complications or local-regional failure. Local infection and implant loss were more frequent in the second than in the first stage (5.2% vs 10.2% and 4.2% vs 12.8%, respectively). Conclusions: Skin bolus significantly increased first-stage breast reconstruction complications (infection and reconstruction failure). Despite the small sample size and the need for future studies, these findings need to be taken into consideration when planning treatment and reconstruction, and recommendations should be individualized.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Prognostic factors in locally advanced cervical cancer with pelvic lymph node metastasis.

OBJECTIVE: To evaluate the prognostic impact of clinical and pathological variables and patterns of recurrence in patients with locally advanced cervical cancer with pelvic lymph node involvement (stage IIIC1 according to the 2018 FIGO Staging System). METHODS: We retrospectively analyzed 62 patients with locally advanced cervical cancer treated with curative intent with radiotherapy associated with chemotherapy in AC Camargo Cancer Center from January 2007 to December 2018. RESULTS: Lymph node involvement was assessed by CT, MRI and positron emission tomography (PET)/CT in 28 (45.2%), 20 (32.3%) and 14 (22.6%) patients, respectively. The median tumor size was 5.0 cm and 72.6% of cases were squamous cell carcinomas. The median number of positive pelvic lymph nodes was three, and the median size of lymph nodes was 24 mm. Twenty-two (35.5%) patients had recurrence and 50% had only one site of recurrence. The sites of recurrence were pelvic, para-aortic and distant in 12 (19.4%), 6 (9.7%) and 16 (25.8%) patients, respectively. The 3 year overall and disease-free survival were 70.8% and 64.6%, respectively. Patients with adenocarcinoma had worse disease-free survival (HR 2.38; 95% CI 1.01 to 5.60; p=0.047) and overall survival (HR 2.99; 95% CI 1.14 to 7.75; p=0.025) compared with squamous cell carcinoma. In multivariate analysis, metastatic pelvic lymph node size of >2.5 cm (HR 4.38; 95% CI 1.65 to 11.6; p=0.003) and incomplete response to radiotherapy (HR 5.14; 95% CI 1.60 to 16.4; p=0.006) maintained the negative impact for overall survival. CONCLUSIONS: We found that pelvic lymph node size and incomplete response to radiotherapy negatively impact overall survival in patients with advanced cervical cancer with pelvic lymph node involvement. This finding may help to stratify risk in this group of patients.

Photodynamic therapy to control oral candidiasis in a pediatric patient undergoing head and neck radiotherapy.

Candida albicans is an opportunistic yeast of the oral microbiome which can cause candidiasis in systemically susceptible individuals, such as those undergoing cancer treatment. The local management of the oral lesions is challenging and may be significantly improved with photodynamic therapy (PDT). PDT consists of an association of light with a photosensitizing agent and oxygen, whose interaction produces reactive oxygen species capable of reducing non-specific microbial contamination without causing side effects. This study aimed to report a case in which oral candidiasis was managed with PDT. A 12-year-old male patient undergoing head and neck radiotherapy (HNRT) for Undifferentiated Mesenchymal Neoplasm presented with dysgeusia, oral pain, and yeast infection on the 13th session of HNRT. The patient used topical antifungals for 30 consecutive days with no lesion or symptom remission. PDT was then proposed and the lesion was healed after a single PDT session, with no further clinical signs of infection and return to normal oral function. Local and non-invasive management of oral candidiasis is of utmost importance for immunocompromised patients, with good acceptability, no systemic side effects, and no drug interactions.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms.

OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms

SUMMARY OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

High-grade gliomas in children and adolescents: is there a role for reoperation?

OBJECTIVE: Tumors of the CNS are the main causes of childhood cancer and have an incidence that exceeds that of leukemia. In addition, they are the leading causes of cancer-related death in childhood. High-grade gliomas account for 11% of such neoplasms and are characterized by aggressive clinical behavior and high morbidity and mortality. There is a lack of studies focusing on the factors that can prolong survival in these patients or guide therapeutic interventions. The authors aimed to investigate the factors related to longer survival durations, with a focus on reoperation for gross-total resection (GTR). METHODS: In this retrospective cohort study, the authors analyzed 78 patients diagnosed with high-grade gliomas occurring across all CNS locations except diffuse intrinsic pontine gliomas. Patients 0 to < 19 years of age were followed up at the Pediatric Oncology Institute. Overall survival (OS) and progression-free survival (PFS) were analyzed in the context of various prognostic factors, such as age, sex, histology, extent of tumor resection, reoperation for GTR, adjuvant treatment, and treatment initiation from 2010 onward. RESULTS: With a mean age at diagnosis of 8.7 years, 50% of the patients were female and approximately 39% underwent GTR at some point, which was already achieved in approximately 46% of them in the first surgery. The median OS was 17 months, and PFS was 10 months. In terms of median OS, the authors found no significant difference between those with reoperation for GTR and patients without GTR during treatment. Significant differences were observed in the OS in terms of the extent of resection in the first surgery, age, sex, Ki-67 expression, adjuvant treatment, and treatment initiation from 2010 onward. Furthermore, the PFS values significantly differed between those with GTR in the first surgery and Ki-67 expression ≥ 50%. CONCLUSIONS: This study demonstrates the importance of GTR for these neoplasms, highlights the role of surgeons in its achievement in the first attempt, and questions the role of reoperation for this purpose. Finally, this study further supports the use of combined adjuvant treatment for the improvement of OS and PFS.

Kidney-sparing whole abdominal irradiation in Wilms tumor: Potential advantages of VMAT technique.

PURPOSE: To present a preliminary clinical experience and a dosimetric comparison of kidney-sparing volumetric modulated arc therapy (VMAT) with three-dimensional conformal radiotherapy (3D-CRT) for whole abdominal irradiation (WAI), in the setting of Wilms tumor (WT) treatment. MATERIALS AND METHODS: From a total of 20 consecutive WT cases treated with adjuvant irradiation, seven were submitted to WAI with VMAT. Renal function and survival rates were evaluated, and, for comparison purposes, similar VMAT and 3D-CRT treatment plans were performed for WAI patients, and differences were dosimetrically evaluated regarding doses to the remaining kidney and other organs at risk and the planning target volume (PTV). RESULTS: After a median follow-up time of 40.8 months (35.3-52.2), no acute significant intestinal toxicity was observed, and median creatinine clearance was 110.1 and 103.3 mL/min/1.73 m², respectively, before treatment and at last follow-up for WAI patients (P = 0.128). For comparative plans, maximum and median doses were lower for the remaining kidney with VMAT than with 3D-CRT. VMAT was associated with better PTV coverage as compared with 3D-CRT, with superior results for all the evaluated parameters (D95, D2, V100%, V98%, V95%; P = 0.018). CONCLUSION: The use of VMAT technique is associated with lower radiation doses to the remaining kidney and better coverage to the PTV than 3D-CRT technique for WAI, with preliminary clinical experience showing a favorable toxicity profile. Long-term results from prospective studies might prove the ability of VMAT to spare renal function in the setting of WT treatment.

Intensity-modulated ventricular irradiation for intracranial germ-cell tumors: Survival analysis and impact of salvage re-irradiation.

BACKGROUND AND PURPOSE: The roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy. MATERIALS AND METHODS: We reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions. RESULTS: Twenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18-30.6 Gy) and 36 Gy (range: 30-54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%. CONCLUSIONS: The results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment.

Intraoperative breast radiotherapy: survival, local control and risk factors for recurrence.

BACKGROUND: Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. AIM: To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. MATERIALS AND METHODS: 147 patients treated with a median follow up of 6.9 years (0.1â¿¿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p â¿¤ 0.05 was considered statistically significant. RESULTS: Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). CONCLUSIONS: IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

Intraoperative radiation therapy for the treatment of recurrent retroperitoneal and pelvic tumors: a single-institution analysis.

BACKGROUND: Patients with recurrent retroperitoneal and pelvic region tumors often require multimodal therapies. Intraoperative radiation therapy (IORT) can deliver high-dose radiation to tumor beds, even if first-line external beam radiation therapy (EBRT) was administered. We evaluated local control (LC) and survival in patients receiving IORT for recurrent tumors. METHODS: We retrospectively analyzed 41 patients with isolated pelvic or retroperitoneal recurrences of colorectal, gynecological, or retroperitoneal primary tumors. Following salvage surgery, all patients underwent tumor bed IORT via electron beam or high dose rate brachytherapy. Isolated IORT (median dose: 15 Gy) was administered to patients who had received first-line EBRT; other patients received IORT (median dose 12 Gy) plus EBRT. Local (LF), regional (RF), and distant failures (DF) were evaluated, and the Kaplan-Meier method and log-rank test were used to evaluate and compare overall survival (OS) from the date of IORT. RESULTS: Forty-one patients underwent 44 treatments, including 27 (61.3%) isolated IORT and 17 (38.7%) IORT and EBRT combination regimens. The median follow-up was 8.1 years (range: 4.4-11.7 years), and the 2, 5, and 8 year overall LC rates were 87.9, 64.0, and 49.8%, respectively. Regarding resection status, the respective 2, 5, and 8 year LC rates were 90, 76, and 76% for R0 resection and 75, 25, and 0% for R1 resection (p < 0.001). The 2, 5, and 8 year OS rates were 68, 43, and 26%, respectively. OS was better among patients with LC (p < 0.001). Twenty-four patients (58.5%) experienced a DF, and the 5 year OS rates for the patients with and without DF were 36 and 52%, respectively (p = 0.04). In a multivariate analysis, LF (p = 0,012) and recurrent retroperitoneal sarcoma (p = 0,014) were identified as significant predictors of worse OS. Thirteen patients (31%) developed clinically treatable complications related to IORT. CONCLUSIONS: Many patients achieve long-term OS and LC without significant morbidity after salvage surgery and IORT, especially in case of clear margins.

Uterine transposition after radical trachelectomy.

Objective: To report the first uterine transposition for fertility sparing in cervical cancer. Methods: We report a 33-year-old woman with stage Ib1 cervical cancer (b2 cm in size) who had a radical trachelectomy that, after the definitive pathological report, fulfilled the criteria for adjuvant radiotherapy. Results: The patient had eggs retrieval and received gosereline 10.8 mg before surgery. The uterine corpus and ovaries were detached from the previous vaginal anastomosis, laparoscopically mobilized, and sutured in the right upper abdominal wall with non-absorbable transparietal suture. The adjuvant external beam radiotherapy (45 Gy) was delivered in the pelvis. One week after, the uterus and ovaries were repositioned and sutured in the vagina. The patient had hospital discharged in the 2° post-operative day and no early complications. After 6 months of follow-up the patient has regular menses and no evidence of recurrence. Conclusions: Uterine transposition is feasible after radical trachelectomy in selected patients who still desire to preserve fertility. However, further studies that address its effectiveness and safety are required.

HER-2 Expression and Response to Radiotherapy in Patients with Advanced Cervical Cancer.

Glauco Baiocchi, M.D., Ph.D., Maria Dirlei Begnami, M.D., Ph.D., Michael Jenwei Chen, M.D., Elza Mieko Fukazawa, M.D., Ph.D., Levon Badiglian-Filho, M.D., Ph.D., Antonio Cassio Assis Pellizzon, M.D., Ph.D., Fernando Augusto Soares, M.D., Ph.D., and Ademar Lopes, M.D., Ph.D. OBJECTIVE: To evaluate HER-2 expression as a predictor of the response to radiotherapy and its value as a prognostic marker. STUDY DESIGN: A retrospective analysis was performed in a series of 34 individuals with advanced stage cervical cancer who underwent radiotherapy followed by radical hysterectomy. HER-2 expression was measured by immunohistochemistry in biopsies from all patients prior to radiotherapy and in 14 patients with residual tumors after radiotherapy. The presence of gene amplification was also examined. RESULTS: Eighteen (53%) patients had residual disease after radical hysterectomy. HER-2 was expressed in 26.5% of cases. Gene amplification by FISH was detected in 2.9% of cases. HER-2 expression was associated with a higher risk of residual disease after radiotherapy (p= 0.019). HER-2 expression did not correlate with the risk of recurrence or death. CONCLUSION: The prevalence of HER-2 expression is low in cervical cancer, and although HER-2 can predict the response to radiotherapy, it does not correlate with poor outcomes.

Unintended irradiation of internal mammary chain - Is that enough?

AIM: To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed. BACKGROUND: The dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions. MATERIALS AND METHODS: One hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques. RESULTS: The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), and breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy, and 18.67 Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). Mean doses to IMC were greater in patients with T3-T4 tumors when compared with more initial stages (≤T2) (p = 0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1 Gy × node negative: 17.8 Gy, p = 0.0017). CONCLUSIONS: The moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy.

Bladder (ICRU) dose point does not predict urinary acute toxicity in adjuvant isolated vaginal vault high-dose-rate brachytherapy for intermediate-risk endometrial cancer.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) alone is an adjuvant treatment option for stage I intermediaterisk endometrial cancer after complete surgical resection. The aim of this study was to determine the value of the dose reported to ICRU bladder point in predicting acute urinary toxicity. Oncologic results are also presented. MATERIAL AND METHODS: One hundred twenty-six patients were treated with postoperative HDR-BT 24 Gy (4 × 6 Gy) per ICRU guidelines for dose reporting. Cox analysis was used to identify variables that affected local control. The mean bladder point dose was examined for its ability to predict acute urinary toxicity. RESULTS: Two patients (1.6%) developed grade 1 gastrointestinal toxicity and 12 patients (9.5%) developed grades 1-2 urinary toxicity. No grade 3 or greater toxicity was observed. The mean bladder point dose was 46.9% (11.256 Gy) and 49.8% (11.952 Gy) for the asymptomatic and symptomatic groups, respectively (p = 0.69). After a median follow-up of 36.8 months, the 3-year local failure and 5-year cancer-specific and overall survival rates were 2.1%, 100%, and 94.6%, respectively. No pelvic failure was seen in this cohort. Age over 60 years (p = 0.48), lymphatic invasion (p = 0.77), FIGO histological grade (p = 0.76), isthmus invasion (p = 0.68), and applicator type (cylinder × ovoid) (p = 0.82) did not significantly affect local control. CONCLUSIONS: In this retrospective study, ICRU bladder point did not correlate with urinary toxicity. Four fractions of 6 Gy HDR-BT effected satisfactory local control, with acceptable urinary and gastrointestinal toxicity.

Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision.

BACKGROUND: To evaluate the local control of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS), correlate the outcome with treatment parameters and lesion characteristics, and define its implications for clinical decisions. METHODS: Between 2007 and 2012, 305 BM in 141 consecutive patients were treated with SRS. After exclusions, 216 BM in 100 patients were analyzed. Doses were grouped as follows: ≤15 Gy, 16-20 Gy, and ≥21 Gy. Sizes were classified as ≤10 mm and >10 mm. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify the prognostic factors affecting LC and OS. For multivariate analyses, a Cox proportional model was applied including all potentially significant variables reached on univariate analyses. RESULTS: Median age was 54 years (18-80). Median radiological follow-up of the lesions was 7 months (1-66). Median LC and the LC at 1 year were 22.3 months and 69.7%, respectively. On univariate analysis, tumor size, SRS dose, and previous whole brain irradiation (WBRT) were significant factors for LC. Patients with lesions >10 and ≤10 mm had an LC at 1 year of 58.6% and 79.1%, respectively (p = 0.008). In lesions receiving ≤15 Gy, 16-20 Gy, and ≥21 Gy, the 1-year LC rates were 39.6%, 71.7%, and 92.3%, respectively (p < 0.001). When WBRT was done previously, LC at 1 year was 57.9% compared with 78.4% for those who did not undergo WBRT (p = 0.004). On multivariate analysis, dose remained the single most powerful prognostic factor for LC. Median OS for all patients was 17 months, with no difference among the groups. CONCLUSIONS: Dose is the most important predictive factor for LC of BM. Doses below 16 Gy correlated with poor LC. The SRS dose as salvage treatment after previous WBRT should not be reduced unless there is a pressing reason to do so.

Ototoxicity evaluation in medulloblastoma patients treated with involved field boost using intensity-modulated radiation therapy (IMRT): a retrospective review.

BACKGROUND: Ototoxicity is a known side effect of combined radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma. The delivery of an involved field boost by intensity modulated radiation therapy (IMRT) may reduce the dose to the inner ear when compared with conventional radiotherapy. The dose of cisplatin may also affect the risk of ototoxicity. A retrospective study was performed to evaluate the impact of involved field boost using IMRT and cisplatin dose on the rate of ototoxicity. METHODS: Data from 41 medulloblastoma patients treated with IMRT were collected. Overall and disease-free survival rates were calculated by Kaplan-Meier method Hearing function was graded according to toxicity criteria of Pediatric Oncology Group (POG). Doses to inner ear and total cisplatin dose were correlated with hearing function by univariate and multivariate data analysis. RESULTS: After a mean follow-up of 44 months (range: 14 to 72 months), 37 patients remained alive, with two recurrences, both in spine with CSF involvement, resulting in a disease free-survival and overall survival of 85.2% and 90.2%, respectively.Seven patients (17%) experienced POG Grade 3 or 4 toxicity. Cisplatin dose was a significant factor for hearing loss in univariate analysis (p < 0.03). In multivariate analysis, median dose to inner ear was significantly associated with hearing loss (p < 0.01). POG grade 3 and 4 toxicity were uncommon with median doses to the inner ear bellow 42 Gy (p < 0.05) and total cisplatin dose of less than 375 mg/m2 (p < 0.01). CONCLUSIONS: IMRT leads to a low rate of severe ototoxicity. Median radiation dose to auditory apparatus should be kept below 42 Gy. Cisplatin doses should not exceed 375 mg/m2.