Standard Postoperative Radiotherapy Research Articles

Prognostic factors in patients with glioblastoma multiforme: focus on the pathologic variants.

The aim of this study was to offer predicting factors for survival in adult patients with glioblastoma multiforme. 153 consecutive patients with high-grade glioma (WHO grade IV) were studied in Imam Reza hospital, Kermanshah University of Medical Science, Kermanshah, Iran, between April 2003 and April 2017. All patients treated with surgical resection and standard postoperative radiotherapy (54Gy). Using the patients' charts and electronic medical records system, the following data were obtained: gender, age, Karnofsky performance status (KPS) score on admission, primary vs. secondary type, extent of surgery, tumor location, tumor size, necrosis size, use of Temozolomide (TMZ), pathology subtype, and immunohistochemistry results. Patients were followed from the time of the surgery until the death occurred. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Survival time curves for various subgroups were compared by the log-rank test. The impact of the suggested prognostic factors on survival was evaluated by univariate and multivariate analyses. Age, gender, KPS, extent of surgery, tumor location, necrosis size, and reoperation in recurrence had not any statistically significant effect on survival. Univariate analysis revealed a significant impact on outcome for pathology subtype (PFS: P < 0.001, OS: P < 0.001), tumor type (primary vs. secondary) (PFS: P = P < 0.001, OS: P < 0.001), tumor size (PFS: P = 0.044, OS: P = 0.04), TMZ therapy (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). In multivariate analysis, independent favorable prognostic factors for survival were pathology subtype (PFS: P < 0.001, OS: P < 0.001), type (PFS: P < 0.001, OS: 0.012), TMZ (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). The results suggest that pathology subtype, primary vs. secondary type, TMZ therapy, P53, and Ki 63 may play an important role in the survival of patients with glioblastoma multiforme. There is no relationship detected between age, gender, KPS, tumor size and location, necrosis size, extent of surgery, reoperation in recurrence, and patient survival.

Comparison of diffusion tensor, dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma

IntroductionTreatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis. MethodsA prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, 99mTc-Tetrofosmin brain SPECT. ResultsBoth 99mTc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between 99mTc-Tetrofosmin uptake ratio and rCBV (P=0.003). ConclusionsDynamic susceptibility contrast MRI and brain SPECT with 99mTc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.

Prevalence of level V metastasis in head and neck squamous cell carcinoma

Conclusion: The results of this study accord with those of past reports about the prevalence of level V metastasis in head and neck squamous cell carcinoma (HNSCC) cases. Because of the low rate of level V metastasis, and from the viewpoint of standard postoperative radiotherapy, selective neck dissection without level V dissection may be possible in cases without clinical evidence of level V metastasis on both the ipsilateral and contralateral sides. In addition, degree of pathological differentiation and pN stage >N2b are suggested risk factors for level V metastasis. Objectives: The most frequent complication of any type of neck dissection in HNSCC cases with level V metastasis is shoulder dysfunction secondary to traction or ischemic injury to the spinal accessory nerve (SAN). The purpose of this study was to examine procedures to preserve the SAN and avoid level V dissection and shoulder dysfunction due to SAN injury. This study investigated the prevalence of level V metastasis and its associated risk factors at various primary sites in patients with HNSCC. Methods: Clinical and pathological data were retrospectively reviewed for 162 patients with HNSCC, including those with clinically negative neck (cN0) and clinically positive neck (cN+) in whom level V neck dissection was performed. The prevalence of pathological metastasis to level V lymph nodes on both the ipsilateral and contralateral sides was investigated. Several potentially predictive risk factors for level V metastasis, such as age, sex, primary site, T stage, N stage, degree of pathological differentiation, and lymph node status of levels I–IV, were also evaluated. Statistical analysis was performed using Fisher's exact test. Results: In total, 301 neck dissections (ipsilateral side, n = 162; contralateral side, n = 139) were performed in this study. The most common primary site was the oral cavity (n = 51), followed by the larynx (n = 48), hypopharynx (n = 39), and oropharynx (n = 24). On the ipsilateral side, the overall incidence of pathologically positive neck (pN+) was 63.6% (103/162). The overall prevalence of level V metastasis was 7.4% (12/162), 6.8% (11/162) on the ipsilateral side, and 1.4% (2/139) on the contralateral side. Isolated level V metastasis and bilateral level V metastasis was observed in three patients and one patient, respectively. Metastasis to level V and other levels was observed in eight patients (8/96, 8.3%), and level V involvement on the ipsilateral side alone was observed only in three patients (3/66, 4.5%). There were two cases in which level V was involved when the other levels were also involved (2/22, 9.1%), and there was no case in which the other levels were not involved on the contralateral side. A statistically significant association was found between level V metastasis and pN stage >N2b (p = 0.0035), degree of pathological differentiation (p = 0.0305) on the ipsilateral side, status of neck levels I–IV (p = 0.001), and the number of positive neck levels (p < 0.0001) on the contralateral side.

Improved survival time trends for glioblastoma using the SEER 17 population-based registries.

2013 Background: The EORTC/NCIC 22981/26981 study demonstrated a significant improvement in median overall survival (OS) from 12.1 to 14.6 months in newly diagnosed glioblastoma (GBM) who received concomitant and adjuvant temozolomide to standard post-operative radiotherapy (RT) (Stupp et al.). The current study was performed to determine if those results have translated into an OS benefit in a population-based cohort. Methods: Patients, ages 20 years and older, who had been diagnosed between January 2000 and December 2006 (follow-up through December, 2007) with a GBM in a brain or central nervous system site and who underwent surgical resection and post-operative RT were selected from the Surveillance, Epidemiology and End Results (SEER) 17 registries research database. Patients were grouped into three time periods for comparison: 2000-2001, 2002-2003, and 2005-2006 (which likely represented the group treated after the EORTC/NCIC trial initial presentation in 2004). OS was estimated by the Kaplan-Meier method, and Cox multivariable regression modeling was used to estimate proportional hazard ratios controlling for potential confounders, such as age, gender, race, extent of surgery, and SEER registry. Results: 7,022 patients were selected with a median follow up of 13 months. Of the cohort, 79.3% received a gross total resection. The median and two year OS for the entire cohort for 2000-2006 was 13 months and 20%, respectively. Over the three time periods studied, there was a significant improvement in the median and 2 year OS of 12 months and 14% for 2000-2001, 13 months and 18% for 2002-2003, and 14 months and 25% for 2005-2006 (p < 0.0001). The estimated adjusted hazard ratio showed that patients diagnosed in 2005-2006 had significantly improved OS when compared to patients diagnosed in earlier time periods (HR = 0.651 95% CI: 0.606 -0.699). Conclusions: The median and 2 year OS of 14 months and 25% in 2005-2006 was similar to the median and 2 year OS of 14.6 months and 26% seen in the EORTC/NCIC phase III study. These results are encouraging and suggest that the improved OS associated with the EORTC/NCIC regimen for GBM patients has successfully been translated to population-based settings.

Postoperative accelerated radiotherapy (POPART) versus conventional postoperative radiotherapy (CPORT) in squamous cell head and neck cancer: A multicenter prospective randomized study of the Dutch Head and Neck Cooperative Study Group.

5508 Background: In head and neck squamous cell carcinoma (HNSCC), the overall treatment time of radiation (OTT) is significantly associated with locoregional control (LRC), which is consistent with rapid repopulation of cancer clonogens during radiotherapy. However, the importance of the OTT in the postoperative setting is less clear. Therefore, the main objective of this phase III study was to determine the value of reduction of the OTT of postoperative radiotherapy in high risk patients primarily treated with surgery. Methods: Patients with HNSCC treated with curative surgery and with high risk factors for locoregional recurrence (i.e., positive surgical margins and/or extranodal spread) were randomly assigned to receive either standard postoperative radiotherapy (SPORT) at 2 Gy/fraction/day, 5 days/week to 66 Gy/33 fractions/7 weeks or postoperative accelerated radiotherapy (POPART) with 2 Gy/fraction/day, 5 days per week, to 20 Gy followed by 1.8 Gy/fraction/day and 1.3 Gy/fraction per day to a boost field as a second daily treatment to 66.5 Gy/40 fractions/5 weeks.The primary endpoint was locoregional tumor control (LRC). Secondary endpoints were overall survival, acute and late toxicity and quality of life. Results: From December 2004 to October 2008, 148 patients were enrolled in the study (74 pts for SPORT and 74 pts for POPART). The two study-arms were well balanced with regard to the most important prognostic factors. No significant differences were noted with regard to acute and late toxicity, although there was a trend towards more use of pain medication among patients treated with POPART. At 3 years, the locoregional control rate was 77% after POPART compared to 76% with SPORT (HR: 0.86, CI 0.42-1.76; p=0.68). The 3-year overall survival rate was 71% with POPART compared to 63% with SPORT (HR:0.93, CI 0.54-1.61; p=0.81). Conclusions: A reduction in the OTT of postoperative radiotherapy in patients with HNSCC with adverse factors for locoregional failure does not improve outcome in terms of locoregional control and overall survival. No significant financial relationships to disclose.

Cervical cancer patients may benefit from new surgical technique

A new surgical technique may help reduce complications and improve recurrence in patients with early-stage cervical cancer, according to a study published in Lancet Oncology.1 Called a total mesometrial resection (TMMR), the techniqne is a modified traditional radical hysterectomy that is more accurate and anatomically based, allowing there to be less damage to the autonomic nerve system and less surgical trauma, according to lead author Michael Höckel, MD, of the University of Leipzig, Germany. Standard hysterectomy has a relatively high rate of recurrence, and many patients have postoperative bowel and bladder dysfunction. In addition, the standard postoperative radiotherapy that is used has a number of side effects, notes Dr. Höckel. Under current guidelines, the standard hysterectomy involves the removal of pelvic tissue adjacent to the tumor along with the cervix. But some experts believe that localized cancer may only spread to the Müllerian compartment (the fallopian tubes, uterus, proximal, middle vagina, and their embryologically defined mesotissues). As a result, they conclude that removing the complete Müllerian compartment in early-stage disease could reduce recurrence and morbidity. To confirm this theory, Dr. Höckel and his colleagues assessed the effectiveness of TMMR without radiotherapy in 212 patients with early-stage cervical cancer who received treatment at the University of Leipzig between 1999 and 2008. They reported recurrence-free survival of 94% and 5-year survival of 96%. At 41 months, 10 patients had, a recurrence of their cancer. The overall recurrence rate was 5% compared with 28% for patients treated with standard radical hysterectomy. Meanwhile, the 5-year survival for patients with positive lymph nodes was 91% compared with 68% treated with the standard technique. In addition, 63% had no treatment-related complications, while 35% and 20% had grade 1 and 2 complications, respectively. No grade 3 and 4 complications were reported. Dr. Höckel and his colleagues conclude that TMMR without adjuvant radiation may improve survival by 15% but that multi-institutional controlled trials must further assess the technique.

In Vivo Intraoperative Radiotherapy: A Novel Approach to Radiotherapy for Early Stage Breast Cancer

Intraoperative radiotherapy (IORT) has the potential to eliminate the access problems associated with standard 6-week post-operative external beam radiotherapy for patients with breast cancer. However, accurate delivery of the IORT dose for breast cancer has been problematic due to difficulty estimating the tumor bed after tumor removal and tissue re-approximation. We are investigating the feasibility of partial breast irradiation using a single fraction of IORT delivered to the tumor in vivo prior to surgical resection. In a trial, approved by the University of North Carolina School of Medicine Institutional Review Board, patients > or =55 years old with infiltrating ductal carcinoma without an extensive intraductal component with an overall tumor size < or =3.0 cm receive a single dose of IORT in place of standard post-operative radiotherapy. All patients undergo preoperative ultrasonography to define the target volume. In a standard operating room, the tumor is exposed through a standard partial mastectomy incision. IORT is then delivered using a mobile, self-shielded, magnetron-driven X-band linear accelerator (Intraop Corp, Santa Clara, CA, USA). 15 Gy is delivered to the 90% isodose line covering the tumor with a 1 cm margin anterior-posterior and 2 cm margins laterally. After IORT, partial mastectomy is performed in the usual manner. IORT for breast cancer, delivered to the exposed tumor in vivo, is feasible and allows accurate estimation of the tumor bed. Further follow-up is ongoing to determine the efficacy of this approach.

Anaplasia Is Rare and Does Not Influence Prognosis in Adult Medulloblastoma

Histopathologic grading based on increasing anaplasia predicts clinical behavior of pediatric medulloblastomas. The present study was aimed at grading 86 medulloblastomas of adult patients (aged 18 and older) by anaplasia and analyzing the predictive power. Nodularity, desmoplasia, nuclear size, nuclear pleomorphism, necrosis, and endothelial proliferations have been evaluated. Morphometric analysis of nuclear size was performed using the Eclipse Net program. Patients treated with standard postoperative radiotherapy (35 Gy to craniospinal axis and 50 Gy to posterior fossa) were considered for correlation with survival. Pathologic data and total survival were compared by Kaplan-Meier and logrank analysis. No correlation was found between total survival duration and individual pathologic features. Cooccurrence of nuclear pleomorphism, large nuclear diameter, microvascular proliferations, and necroses did not predict outcome. Severe nuclear pleomorphism was found in 4 of 86 cases; the only large-cell medulloblastoma was from an 18-year-old patient. Histopathologic factors have no clinical use for stratification of patients in risk groups. The histologic spectrum of medulloblastoma in adults is different from that in children.

Results of treatment intensification for progressive locoregional disease in head-and-neck cancer patients undergoing postoperative radiotherapy

Patients who develop progressive locoregional disease during radical surgery and postoperative radiotherapy for squamous cell carcinoma of the head and neck represent a management dilemma. We present our experience using treatment intensification for such patients. A prospective record of eligible patients was kept between May 1998 and December 2001. The study included 15 patients, 11 men and 4 women (median age, 60 years); 67% had Stage III-IV disease. The sites of progression were primary in 3, nodes/scar in 10, and both primary and nodes in 2. Relative to the initial plan, treatment intensification was achieved by an increased radiation dose in 7 (using accelerated fractionation in 5), an increased radiation dose and the addition of concomitant chemotherapy in 7, and the addition of concomitant chemotherapy alone in 1 patient. The median follow-up was 40 months. Eight patients had a complete response to intensified treatment. At the closeout date, 6 patients were alive with no evidence of disease. Eight patients had died with locoregional disease; two also had distant metastases. One patient was lost to follow-up after achieving a complete response. The median failure-free survival for all patients was 6 months, but for those with a complete response, it was 37 months. The median overall survival time was 28 months. The 2-year and 3-year overall survival rate was 50% and 42%, respectively. Acute mucosal and skin toxicity was increased relative to standard postoperative radiotherapy but was not dissimilar to that expected after radical definitive chemoradiotherapy. Intensification of treatment in patients who develop progressive locoregional disease is warranted, because it can lead to long-term disease control in a subset of patients with significant but acceptable toxicity.

Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome

To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.