Actuarial Overall Survival Rates Research Articles

Ten-Year Outcomes and Toxicity with Moderately Hypofractionated (70 Gy in 28 fractions) Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

Long-term outcomes with hypofractionated radiation therapy for prostate cancer are limited. We report 10-year efficacy and toxicity outcomes of patients treated with intensity modulation radiation therapy (IMRT) for localized prostate cancer with 70 Gy in 28 fractions at 2.5 Gy/fraction. This IRB-approved study included all 854 consecutive patients with localized prostate cancer treated with moderately hypofractionated IMRT at a single institution between 1998 and 2012. The median follow-up was 11.3 years (maximum, 19 years). Patients were grouped into low-risk (LR, n=266); favorable intermediate-risk (FIR), defined as a single National Comprehensive Cancer Network (NCCN) intermediate-risk factor (n=238); unfavorable intermediate-risk (UIR), defined as ≥2 NCCN intermediate-risk factors (n=106), and high-risk (HR, n=244) groups. Biochemical relapse free survival (bRFS; defined as nadir + 2 ng/mL), clinical relapse free survival (cRFS), & overall survival (OS) were analyzed used Kaplan-Meier analysis. Prostate cancer specific mortality (PCSM) was analyzed using Fine and Gray regression. All grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using CTCAE version 4.03 and cumulative incidence rates of GU and GI toxicity were calculated. The 10-year bRFS was 71% (95% CI: 67-74%). For patients with LR, FIR, UIR, and HR disease the 10-year bRFS rates were 88%, 78%, 71%, and 42%, respectively (p <0.0001), while the 10-year cRFS rates were 95%, 91%, 85%, and 72%, respectively (p <0.0001). Overall, the 10-year actuarial OS rate was 69% (95% CI: 66-73%) and the 10-year PCSM was 7% (95% CI: 5-9%). For patients with LR, FIR, UIR and HR disease, the 10-year PCSM rates were 2%, 5%, 5% and 15%. Long-term grade ≥3 GU or GI toxicity remained low with 10-year cumulative incidences of 2% and 1%, respectively. High-dose moderately hypofractionated IMRT for localized prostate cancer continues to show excellent oncological outcome with a low incidence of toxicity over long-term follow up. This fractionation schedule appears to be acceptable for patients across all risk groups.

Outcomes Following Salvage Radiation and Systemic Therapy for Isolated Locoregional Recurrence of Breast Cancer after Mastectomy: Impact of Constructed Biologic Subtype.

Purpose This study examines factors associated with outcomes following salvage radiation and systemic therapy for breast cancer patients who developed isolated locoregional recurrence (ILRR) after mastectomy alone, while focusing on the prognostic significance of constructed biologic subtype in this setting. Methods and Materials 269 postmastectomy patients in total treated for ILRR were included. Cumulative incidence of locoregional control (LRC), distant metastasis (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated using Kaplan-Meier method. For statistical analysis, biologic subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic-pathological and treatment-related parameters with outcomes was evaluated using a Cox regression model. Results At a median follow-up of 65 months, 56 (20.8%) patients failed to secure LRC after radiotherapy, and 165 patients (61.3%) developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was 77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that constructed biologic subtype represented the most significant prognostic factor for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec-/HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P < 0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28, P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus 22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no radical surgery and involved field irradiation alone, whereas factors associated with poor survivals included positive nodes at primary diagnosis and regional recurrence. Conclusions Constructed biologic subtypes remained to be predictive of both disease control and survivals after salvage radiation for postmastectomy ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of locoregional failure and subsequent DM and tended to have worse survivals despite salvage therapies.

Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors.

We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation. Between 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3-174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2-253.6 Gy10) and the prescribed PTV BED10 ranged 23.6-151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (>5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Median follow-up was 14.5 months (1-72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05-0.63, p = 0.01), GTV/PTV (HR 1.01-1.02, CI 1.01-1.04, p < 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97-0.99, CI 0.96-0.99, p < 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p < 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1-2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur. Robotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible.

(P23) Toxicity of Post-Operative Intensity Modulated Radiation Therapy in Patients With Endometrial Cancer

The purpose of this study was to evaluate the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity of post-operative intensity modulated radiation therapy (IMRT), delivered in 160cGy daily fractions, for patients with endometrial cancer. This retrospective study included 103 patients treated between 2006-2016 for endometrial cancer. All patients underwent a surgical staging with central review of pathology. Indications for post-operative IMRT included histology subtype, histological grade, advanced age, lymphovascular space invasion, depth of myometrial invasion, and/or lymph node involvement. All patients received IMRT interdigitated with weekly high-dose rate intracavitary brachytherapy (BT). The median IMRT dose, delivered in 160 cGy daily fractions, was 5120 cGy (range, 3520-5120). The median BT dose prescribed to the vaginal surface, delivered in six weekly fractions, was 2400 cGy (range, 1200-4800). A total of 86 (78%) patients received chemotherapy at the discretion of the treating gynecologic oncologist. The rate of GU and GI toxicities, overall survival (OS), distant free survival (DFS), and local control (LC) were calculated via Kaplan-Meier method. The log-rank test and Cox proportional hazard models were used to evaluate the impact of collected parameters on OS. The median follow-up was 25.2 months (range, 1.3-25.2). The median age at diagnosis was 61 years (range, 36-85). The FIGO pathologic stages were IA in 6 patients, IB in 11, IC in 13, II in 8, IIIA in 2, IIIC1 in 39, and IIIC2 in 24 patients. Histological subtypes included endometrioid adenocarcinoma (n=68), carcinosarcoma (n=14), clear cell (n=2), serous (n=9), and mixed histology (n=10). There were no acute grade > 3 GU or GI toxicities as well as no late grade > 3 GU toxicities. Late grade > 3 GI toxicity occurred in 2 patients; both developed a small bowel obstruction (SBO) with one requiring surgical intervention and the other requiring gastrostomy tube placement. Both of these patients received concurrent chemotherapy. The 2-year actuarial rate for grade ≥3 GI toxicity was 2.5%. The 2-year actuarial rates for OS, DFS, and LC were 84.7 %, 69.8% and 87.1%, respectively. On multivariate analysis non-endometrioid histology (HR 2.53, 95% CI 0.97-6.91, p = 0.07) was predictive of worse OS. Post-operative IMRT for endometrial cancer patients delivered in 160 cGy daily fractions is associated with excellent outcomes and limited rates of radiation-related GU and GI toxicities.

The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy

To analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and progression-free survival (PFS) in patients receiving definitive RT for laryngeal and oropharyngeal cancers. We identified 352 patients with non-metastatic laryngeal (146) and oropharyngeal (206) cancer treated with definitive RT between 2004 and 2013. Disease and patient characteristics, treatment information, sarcopenia based on muscle areas at L3 level on CT, compliance with the nutritional program, and clinical outcomes data were tabulated. Descriptive statistics, Kaplan-Meier survival analysis, and log rank tests were performed, and Cox regression models were used to examine predictors of OS and PFS. The median follow-up for the entire cohort was 22.86months. The actuarial rates for OS were 91, 86, and 73% at years 1, 2, and 5, respectively. Of patients with abdominal CT prior to starting RT, 70.9% (112/158) were sarcopenic with a median muscle mass index of 48.2 (range 30.4-70.9) for males and 35.9 (range 24.6-53.2) for females. The majority (85.8%) of patients met with a dietitian during their course of RT and 62.6% of these patients were compliant with the nutritional program. Compliance with the nutritional program resulted in 27% (HR 0.73, 95% CI 0.43-1.26) protection from death (did not reach significance) and 31% (HR 0.69, 95% CI 0.50-0.94) significant protection from disease progression. Higher pretreatment BMI was associated with a lower risk of death (HR 0.94, 95% CI 0.90-0.99) and disease progression (HR 0.96, 95% CI 0.93-0.99). Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with regular dietetic counseling and contact appear to have improved outcomes. Not applicable.

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages

BackgroundWe sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer.MethodsFrom July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages.ResultsPreoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages.ConclusionPretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

Head and neck cancer reirradiation with interstitial high-dose-rate brachytherapy.

As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation. Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis. For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities. Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.

Evaluation of DNA ploidy with intraoperative flow cytometry may predict long-term survival of patients with supratentorial low-grade gliomas: Analysis of 102 cases

ObjectiveThe objective of the present study was evaluation of the prognostic significance of DNA ploidy assessed with intraoperative flow cytometry (iFC) during resection of low-grade gliomas (LGG). Patients and methodsRetrospective analysis of 102 consecutive cases of newly diagnosed WHO grade II supratentorial gliomas, surgical removal of which was accompanied by iFC, was done. There were 46 diffuse astrocytomas (DA) and 56 oligodendrogliomas (OD). According to iFC, 68 tumors (67%) were considered non-aneuploid and 34 (33%) aneuploid. Median extent of resection (EOR) was 95% (mean, 89.0 ± 14.5%). Postoperative FRT with or without adjuvant chemotherapy was administered in 24 cases (24%). ResultsWith median follow-up of 29.9 months (range, 9.4–66.9 months), neither median overall survival (OS) nor median progression-free survival (PFS) were reached. The 3-year actuarial OS and PFS rates were 95.8% and 86.3%, respectively. Non-aneuploid DNA histogram type of the tumor was associated with significantly longer OS both in univariate (P = 0.0094) and multivariate (P = 0.0232) analyses, and with longer PFS in univariate analysis (P = 0.0184). Aneuploidy was encountered more frequently in DA, than in OD (43% vs. 25% of cases; P = 0.0488). Tumor progression was noted in 15 DA and 4 patients succumbed to the disease; in this subgroup the main unfavorable prognostic factors for OS and PFS were presence of aneuploidy (P = 0.0510) and MIB-1 index ≧3.9% (P = 0.0141), respectively. Aneuploid DA more frequently progressed to glioblastoma than to anaplastic astrocytoma, but this difference did not reach statistical significance (P = 0.1362). In contrast, only one OD progressed (non-aneuploid neoplasm), and no one patient with such tumor died of the disease. ConclusionsDNA ploidy assessed with iFC may be effectively used as prognostic indicator in cases of LGG, especially of DA. Aneuploid tumors demonstrate more aggressive clinical course translated into shorter OS of patients. Thus, their detection during surgery may be helpful for decision on the optimal EOR, and for choice of the most appropriate postoperative adjuvant therapy.

Retrospective long-term results and prognostic factors of postoperative treatment for UICC stages II and III rectal cancer.

To retrospectively evaluate 5-year local control, disease-free survival, cancer-specific survival and overall survival rates in patients with UICC stages II and III rectal cancer treated with adjuvant therapy and especially to analyze the impact of some prognostic factors on clinical outcome at univariate and multivariate analyses. We retrospectively reviewed 306 patients treated with postoperative 5-fluorouracil-based chemoradiation (278 patients) or radiotherapy alone (28 patients) after curative surgery. The following prognostic factors were considered at univariate and multivariate analyses: age, sex, tumor location, surgery procedure, pathological stage, histology, tumor grade, surgical margins and radiotherapy technique. The 5-year actuarial rates for local control, disease-free survival, cancer-specific survival and overall survival were respectively 89.7%, 59.7%, 68.6% and 61.4% for the 278 patients (91%) treated with postoperative chemoradiation. Univariate analysis showed that abdominal-perineal resection impacted disease-free survival and that the T4 variable had an impact on cancer-specific survival and disease-free survival. Instead, age > or = 70, N2, IIIB (p T3 p N1) and IIIC (p T3 p N2) stage impacted cancer-specific survival, disease-free survival and rate of distant metastases. Multivariate analysis showed as significant variables age > or = 70 years, pN1 and pN2 and extraperitoneal tumor location. Our retrospective study showed a good 5-year local control. Factors such as individual pT4, pN1, pN2, age > or = 70 years, abdominal-perineal resection, stages IIIB-IIIC versus II-IIIA and extraperitoneal tumor location negatively influenced disease-free survival, distant metastases and cancer-specific survival. Differences exist between stages II and III rectal cancer and treatment modulation and intensification are required in order to offer the most appropriate and effective adjuvant treatment and to improve survival of rectal cancer patients.

Positron Emission Tomography–Adjusted Intensity Modulated Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Toperform a prospective trial examining positron emission tomography (PET)-based, dose-painted intensity modulated radiation therapy (IMRT) in the setting of locally advanced non-small cell lung cancer (NSCLC). Patients with stage IIB-III NSCLC were treated with 25 fractions of dose-painted IMRT. Tumors or lymph nodes with metabolic tumor volume exceeding 25cm3 were deemed "high risk" and received 65Gy. Smaller lesions were treated with 57Gy or 52.5Gy (after November 2014). Patients received concurrent weekly carboplatin (area under the curve=2) and paclitaxel (45mg/m2). The primary study endpoint was the absence of high residual metabolic activity (maximum standardized uptake value>6) in treated lesions on PET 12 to 16weeks after completion of IMRT. Thirty-five subjects with 116 hypermetabolic lesions were eligible for analysis. The primary endpoint was met for 24 of 30 patients (80%) who underwent posttreatment PET, satisfying our efficacy objective. With a median follow-up duration of 23.8months for living patients, progression in a lesion targeted with radiation therapy has been observed in 5 patients (14%). Treating progression in other sites and death without progression as competing risks, 2-year cumulative incidence rates of local disease progression in high-risk lesions (n=24) and low-risk lesions (n=92) are 9% and 3%, respectively. The actuarial rate of overall survival at 2years is 52%. Dose-painted IMRT based on pretreatment PET metrics with concurrent chemotherapy yields high rates of metabolic response and local disease control for locally advanced NSCLC. Future trials should test this approach to maximize the therapeutic ratio of thoracic radiation therapy.

Surgical management of incidentally discovered diffusely infiltrating low-grade glioma.

OBJECTIVE Occasionally, diffusely infiltrating low-grade gliomas (LGGs) are identified as incidental findings in patients who have no signs or symptoms that can be ascribed to the tumors. The diagnosis of incidental, asymptomatic LGGs has become more frequent due to the vast increase in access to medical imaging technology. While management of these lesions remains controversial, early surgery has been suggested to improve outcome. The authors set out to identify and review the characteristics and surgical outcomes of patients who underwent surgical intervention for incidental LGG. METHODS All cases of LGG surgically treated between 2004 and 2016 at the authors' institution were analyzed to identify those that were discovered incidentally. Patients with incidentally discovered LGGs were identified, and their cases were retrospectively reviewed. An "incidental" finding was defined as an abnormality on imaging that was obtained for a reason not attributable to the glioma, such as trauma, headache, screening, or research participation. Kaplan-Meier analysis was performed to determine actuarial rates of overall survival, progression-free survival, and malignant progression-free survival. RESULTS In 34 (6.8%) of 501 adult patients who underwent surgery for LGG, the tumors were discovered incidentally. Headache (26%, n = 9) and screening (21%, n = 7) were the most common indications for brain imaging in this group. Four of these 34 patients had initial biopsy after the tumor was identified on imaging. In 5 cases, the patients opted for immediate resection; the remaining cases were managed with a "watch-and-wait" approach, with intervention undertaken only after radiological or clinical evidence of disease progression. The mean duration of follow-up for all 34 cases was 5 years. Twelve patients (35.3%) had disease progression, with an average time to progression of 43.8 months (range 3-105 months). There were 5 cases (14.7%) of malignant progression and 4 deaths (11.8%). Oligodendroglioma was diagnosed in 16 cases (47%) and astrocytoma in 15 (44%). Twenty-five patients (74%) had IDH1 mutation and demonstrated prolonged survival. Only 2 patients had mild surgery-related complications, and 16 patients (47%) developed epilepsy during the course of the disease. CONCLUSIONS In this retrospective analysis of cases of incidentally discovered LGGs, the tumors were surgically removed with minimal surgical risk. In patients with incidental LGGs there is improved overall survival relative to median survival for patients with symptomatic LGGS, which is likely attributable to the underlying favorable biology of the disease indicated by the presence of IDH1 mutation in 74% of the cases.

A Prospective Outcomes Study of Proton Therapy for Skull-Base Chondrosarcomas

To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on local control and survival in patients with base of skull chondrosarcoma. Between January 2007 and February 2016, 43 patients with a median age of 49 years (range, 23 - 80 years) with base of skull chondrosarcoma were treated with double-scattered proton therapy on an IRB-approved prospective outcomes protocol at our institution. The median total dose delivered was 73.8 Gy(RBE) [range, 64.5 - 74.4 Gy(RBE] with 33 patients treated with 1.8 Gy(RBE) daily fractionation and 10 patients treated with 1.2 Gy(RBE) twice daily fractionation. Primary site included skull base tumors involving the clivus, cavernous sinus, petrous bone, sella, and tumors involving the ethmoid or sphenoid sinuses. Surgical resection and biopsy alone were performed in 36 (83.7%) and 7 (16.3%) patients respectively. Tumor grade was as follows: 19 (44.2%) grade 1, 22 (51.1%) grade 2, and 2 (4.7%) grade 3. Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following initial surgery. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. The median follow-up time was 3.7 years (range, 0.7 -10.1 years). The 3-year actuarial rate of overall survival was 95%; cause-specific survival was 100%, disease-free survival was 93%, local control was 93%, and freedom from distant metastases was 100%. Across all time points, 3 patients experienced local recurrence with no regional or distant recurrence observed. At the time of last follow-up, 38 patients were alive with no evidence of recurrent disease, 2 patients were alive with recurrent disease, 2 patients were dead from intercurrent disease, and 1 patient was dead of recurrent disease. The time to local progression was 2 years, 2.5 years, and 3 years (n = 3) following proton therapy. We did not observe any ≥ grade 3 acute toxicities. 9.3% (n=4) of patients experienced ≥ 3 grade late toxicity following proton therapy: grade 3 hearing loss (n = 3) and a grade 3 radiation-induced tumor consisting of a meningioma 9 years 9 months after treatment. We observed a grade 2 temporal lobe and brainstem radiation necrosis, both occurring in the same patient. High-dose, conformal proton therapy alone or following surgical resection for skull base chondrosarcoma is an effective treatment with a high rate of local control and with a relatively low toxicity profile. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Safety and Efficacy of Treatment of Malignant Pleural Mesothelioma with Imprint Radiation Therapy Using VMAT Following Pleurectomy/Decortication

In the treatment of malignant pleural mesothelioma (MPM), there is evidence to support the use of pleurectomy/decortication (P/D) for surgical resection. This presents a unique challenge to the radiation oncologist to treat the pleura and chest wall while minimizing radiation dose to the underlying lung. Treatment with Intensity-Modulated Pleural Radiation Therapy (IMPRINT) has previously been shown to be efficacious and safe (Rimner et al. J Clin Oncol 2016). It has been shown that Volumetric Modulated Arc Therapy (VMAT) provides superior sparing of critical organs with reduced monitor units (MU) and delivery time when compared to IMRT, while adequately covering the planning target volume (PTV) (Dumane et al. Applied Rad Onc 2016). In this study we evaluated the safety and efficacy of treating this population with IMPRINT using VMAT at our institution. We identified 40 patients at our institution who underwent P/D followed by adjuvant radiation therapy (RT) from 2010-2016. VMAT typically included a minimum of 2 complementary co-planar arcs to cover the PTV. Electronic Medical Records were reviewed for toxicity, recurrence and survival data. Statistical analysis was performed using the Life Table method. The cohort included 26 men and 14 women. 73% had epithelial histology, 3% - sarcomatoid, 23% - mixed and 3% - pleomorphic/anaplastic. The median follow up time was 14.5 months (range 3-42 months). The median radiation dose delivered was 45 Gy (range, 30 – 54 Gy). Chemotherapy (pemetrexed/platinum doublet) consisted of: none (33%), induction (20%), adjuvant (23%). 15% of patients received chemotherapy following surgery but prior to the initiation of RT. The majority of patients (60%) began RT within one month following surgical resection. 70% of patients had an R1 resection and 30% had an R2 resection prior to radiation treatment. The most common adverse effect was fatigue: 80%, 12.5% and 7.5% of patients reported grade 1, 2 or 3 fatigue respectively. 62.5%, 35% and 2.5% of patients reported grade 1, 2 or 3 nausea respectively. Six patients (15%) developed grade 2 or 3 pneumonitis and 1 patient (3%) had grade 5 pneumonitis. 2 patients (5%) developed grade 2 or 3 pericarditis. The 1- and 2-year actuarial rates of overall survival were 62.5% and 17.5%, respectively. The 1- and 2- year actuarial rates of recurrence-free survival were 52.5% and 12.5%, respectively. This is the largest analysis to date of treatment outcomes with adjuvant radiation therapy with IMPRINT using VMAT following pleurectomy/decortication. VMAT provides a reduction in treatment time and improves sparing of critical structures. Our data demonstrate that treatment with this technique is well tolerated and survival is comparable with previous reports.

Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience.

Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990-2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT±BT, with 13.6% receiving BT alone. With a median follow-up of 64.6months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases.

Spine stereotactic radiosurgery for metastatic sarcoma: patterns of failure and radiation treatment volume considerations.

OBJECTIVE Given the relatively lower radiosensitivity of sarcomas and the locally infiltrative patterns of spread, the authors sought to investigate spine stereotactic radiosurgery (SSRS) outcomes for metastatic sarcomas and to analyze patterns of failure. METHODS The records of 48 patients with 66 sarcoma spinal metastases consecutively treated with SSRS between 2002 and 2013 were reviewed. The Kaplan-Meier method was used to estimate rates of overall survival (OS) and local control (LC). Local recurrences were categorized as occurring infield (within the 95% isodose line [IDL]), marginally (between the 20% and 95% IDLs), or out of field. RESULTS Median follow-up time was 19 months (range 1-121 months), and median age was 53 years (range 17-85 years). The most commonly treated histology was leiomyosarcoma (42%). Approximately two-thirds of the patients were treated with definitive SSRS (44 [67%]) versus postoperatively (22 [33%]). The actuarial 1-year OS and LC rates were 67% and 81%, respectively. Eighteen patients had a local relapse, which was more significantly associated with postoperative SSRS (p = 0.04). On multivariate modeling, receipt of postoperative SSRS neared significance for poorer LC (p = 0.06, subhazard ratio [SHR] 2.33), while only 2 covariates emerged as significantly correlated with LC: 1) biological equivalent dose (BED) > 48 Gy (vs BED ≤ 48 Gy, p = 0.006, SHR 0.21) and 2) single vertebral body involvement (vs multiple bodies, p = 0.03, SHR 0.27). Of the 18 local recurrences, 14 (78%) occurred at the margin, and while the majority of these cases relapsed within the epidural space, 4 relapsed within the paraspinal soft tissue. In addition, 1 relapse occurred out of field. Finally, the most common acute toxicity was fatigue (15 cases), with few late toxicities (4 insufficiency fractures, 3 neuropathies). CONCLUSIONS For metastatic sarcomas, SSRS provides durable tumor control with minimal toxicity. High-dose single-fraction regimens offer optimal LC, and given the infiltrative nature of sarcomas, when paraspinal soft tissues are involved, larger treatment volumes may be warranted.

Stereotactic radiosurgery for brain metastases from primary head and neck carcinomas: a retrospective analysis.

Patients with head and neck malignancies commonly develop metastatic disease, yet rarely do these carcinomas metastasize to the brain. Stereotactic radiosurgery (SRS) is routinely employed to treat brain metastases (BM). This study was undertaken to examine the efficacy of SRS for BM from primary head and neck carcinomas. From 2000 to 2016, a total of 19 patients with 38 lesions were retrospectively identified. All patients presented with a primary head and neck malignancy and subsequently developed metastatic disease to the brain treated with SRS at our institution. Actuarial rates for overall survival (OS), local control (LC) and distant brain metastases (DBM) were calculated using Kaplan-Meier estimates. Median follow up was 6.8 months and median survival was 15.8 months. Eleven lesions received post-operative SRS to a surgical cavity and 27 lesions received definitive SRS to a metastasis. The median dose prescribed was 18Gy. One-year actuarial rate for LC was 77.3% (95% confidence interval [CI] 44-92%) while 1year and 2 year rates of OS were 52.9% (CI 28-73%) and 31.7% (CI 11-55%) respectively. The median time to develop DBM was 8.4 months. Three patients (16%) underwent repeat SRS following development of new BM and three patients (16%) underwent salvage whole brain radiotherapy (WBRT). SRS may be utilized in the treatment of patients with primary head and neck malignancies metastasized to the brain with high efficacy. Patients with well-controlled systemic disease and good performance status may benefit the most from definitive SRS while avoiding WBRT.

Treatment Outcome in Patients with Primary Central Nervous System Germ Cell Tumour: Clinical Experience from a Regional Cancer Centre in North India

Background: Primary intracranial germ cell tumour is a rare entity and constitutes 2-3% of all paediatric brain tumours in Western countries. We herein intend to report the clinical features and treatment outcome of patients with primary central nervous system germ cell tumour treated at our institute. Methods: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed and relevant immunohistochemistry stains were done. Overall survival (OS) and progression-free survival (PFS) were analysed by the Kaplan-Meier product-limit method. Results: Twenty patients met the study criterion (male:female = 7:3). Median age at presentation was 13 years. Tumour location was pineal in 10 patients, suprasellar in 6, thalamic in 2, basal ganglion in 1, and spinal in 1. Leptomeningeal spread was noted in 1 patient at presentation. Surgical resection was gross-total in 7 patients (35%), near-total in 2 (10%), subtotal in 4 (20%), and limited to biopsy in 6 (30%). The tumours were germinomatous, non-germinomatous, and of mixed germ cell subtype in 17 patients (85%), 2 patients (10%), and 1 patient (5%), respectively. Systemic chemotherapy (median of 4 cycles) was given to 19 patients (95%). The common regimens used were a combination of bleomycin, etoposide and cisplatin (BEP) in 14 patients (70%) and etoposide and cisplatin (EP) in 5 patients (25%). Radiation therapy (40-50 Gy in conventional fractionation; median of 42 Gy) was delivered to 17 patients (85%): local radiation in 6 and whole ventricular, whole brain, and craniospinal irradiation followed by a boost in 5, 3, and 3 patients, respectively. After a median follow-up of 44.52 months, 17 patients (85%) were in complete response and 3 (15%) had progressive disease. Death and disease recurrence were noted in 6 patients (30%) and 1 patient, respectively. Median OS and PFS were not reached. The actuarial rates of OS at 3 and 5 years were 75.8 and 68.9%, respectively. The actuarial rates of PFS at both 3 and 5 years were 81.6%. Conclusion: Multimodality treatment consisting of limited resection followed by platinum-based systemic chemotherapy and radiotherapy (40-50 Gy) is a reasonable treatment strategy in patients of primary central nervous system germ cell tumour in a developing nation.

Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23–4,993 days), and the median duration of patient follow-up was 256 days (range, 11–2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17–240 Gy2; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.

(P044) Toxicity of Post-Operative Intensity Modulated Radiation Therapy in Patients With Cervical Cancer

The purpose of this study was to evaluate the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity of post-operative intensity modulated radiation therapy (IMRT), delivered in 160cGy daily fractions, for cervical cancer. This retrospective study included 38 patients treated between 2006-2016 with radical hysterectomy, lymphadenectomy, and post-operative IMRT for cervical cancer. Indications for radiation included large tumor size, deep invasion, lymphovascular space invasion, nodal involvement, positive margins, and parametrial involvement. A total of 36 (94.7%) patients received IMRT interdigitated with brachytherapy (BT) and 2 (5.3%) received IMRT alone. The median IMRT dose, delivered in 160 cGy daily fractions, was 5120 cGy (range, 4800-5120). The median BT dose prescribed to the vaginal surface, delivered in six weekly fractions, was 2400 cGy (range, 1200-4800). The rate of GU and GI toxicity, overall survival (OS), distant free survival (DFS), and local control (LC) were calculated via Kaplan-Meier method. The median follow up was 57 months (range, 1.0-123.0) and age at diagnosis was 47 years (range, 23-73). The FIGO clinical stages were IB1 in 29 patients and IB2 in 9 patients. Histological subtypes were adenocarcinoma (n=11), squamous cell carcinoma (n=22), small cell (n=3), and adenosquamous carcinoma (n=2). Concurrent chemotherapy was delivered in 25 (65.8%). There were no acute grade > 3 GU or GI toxicities. Late grade > 3 occurred in 2 patients, including a SBO and a ureteral stricture. The patient with the ureteral stricture also had local tumor recurrence causing ureteral compression. The 5-year actuarial rate for GI and GU toxicity were 2.9% and 3.8%. The 5-year actuarial rates for OS, DFS, and LC were 88.6%, 76.6% and 88.8%, respectively. Post-operative IMRT for patients with cervical cancer delivered in 160 cGy daily fractions is associated with excellent outcomes and limited rates of radiation-related GU and GI toxicity.

Single Fraction Stereotactic Radiosurgery for Retreatment of Skull Base Recurrent Head and Neck Malignancies.

IntroductionRecurrent head and neck carcinomas are notoriously difficult to treat. Salvage surgery, brachytherapy, and repeat external beam radiotherapy have all been utilized, achieving modest local control at the expense of elevated toxicity. We performed a retrospective review to evaluate the efficacy of single fraction stereotactic radiosurgery (SRS) for the treatment of recurrent head and neck carcinomas.MethodsEighteen previously irradiated patients diagnosed with a locoregionally recurrent head and neck malignancy and treated with single fraction SRS from 2000 to 2016 were analyzed. Actuarial rates for local control (LC) and overall survival (OS) were calculated with Kaplan-Meier estimates.ResultsMedian follow-up was 16.1 months and SRS dose was 13.3 Gy. One-year rate of LC was 52.7% (95% confidence interval [CI] 29%-72%). Median OS was 25.4 months. Parotid gland primary had an increased risk of progressive disease (PD) following SRS (hazard ratio [HR] 4.24, p=0.02). Squamous cell histology was negatively associated with OS (HR 3.85, p=0.03). One patient experienced grade 2 radionecrosis.ConclusionsSingle fraction SRS is an acceptable treatment for previously irradiated patients with recurrent head and neck primary malignancies. Dose escalation to optimize LC should be examined.