Efficacy Of Adjuvant Radiotherapy Research Articles

Prognostic factors for mesenchymal chondrosarcoma.

Mesenchymal chondrosarcoma (MCS) is a malignant, biphasic, high-grade, primitive mesenchymal tumor that has a well-differentiated, organized hyaline component. MCS has a poor prognosis, and treatment recommended for localized MCS is based on wide resection while controversy remains regarding the efficacy of adjuvant chemotherapy and radiotherapy. In this study, we aimed to investigate the prognostic factors of MCS, especially the efficacy of adjuvant chemotherapy and radiotherapy for localized MCS. Eighty patients with MCS pathologically diagnosed between 2006 and 2022 from the Japanese National Bone and Soft Tissue Tumor Registry database were analyzed retrospectively. Patients with distant metastases at presentation (n = 23) had significantly shorter survival than those without (n = 57) (5-year disease-specific survival 19.9% [95% confidence interval (CI): 5.6-50.7] vs. 79.8% [95% CI: 62.4-90.4]; p < 0.0001). In the group without distant metastasis at presentation (n = 57), R1 or R2 surgical margin was a risk factor for unfavorable local recurrence (hazard ratio (HR): 17.44 [95% CI: 2.17-139.98]; p = 0.007). There was no correlation between adjuvant radiotherapy and local recurrence rate (HR 5.18 [95% CI: 0.99-27.12]; p = 0.051). R1 or R2 surgical margin was a risk factor for unfavorable disease-specific survival (HR 17.42 [95% CI: 2.18-138.90]; p = 0.007). There was no correlation between adjuvant chemotherapy and disease-specific survival (HR 0.99 [95% CI: 0.28-3.47]; p = 0.990). Patients with MCS and distant metastases at presentation have a poor prognosis, and wide resection is important for the treatment of localized MCS. The efficacy of adjuvant radiotherapy and chemotherapy could not be determined because of the small number of patients.

Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma - A 13-years experience from a tertiary care centre.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival. A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant. The median age of patients was 37.5 years (range, 5-72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse. ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.

Prognostic analysis and beneficiary identification of adjuvant external beam radiotherapy for stage pT4b sigmoid colon cancer

The clinical efficacy of adjuvant radiotherapy in sigmoid colon cancer remains questioned. To evaluate the clinical efficacy of adjuvant external beam radiotherapy (EBRT) for patients with pathologic stage T4b sigmoid colon cancer. Patients with stage pT4b sigmoid colon cancer receiving adjuvant EBRT or not followed by surgery between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. Analysis of overall survival (OS) was performed using Kaplan–Meier curves and prognostic factors were identified using Cox proportional hazards regression models with 95% confidence intervals within the entire cohort. A risk-stratification system was then developed based on the β regression coefficient. Among 2073 patients, 284 (13.7%) underwent adjuvant EBRT. The median OS in the group receiving adjuvant EBRT was significantly longer than that in the non-radiotherapy group (p < 0.001). Age, serum carcinoembryonic antigen (CEA) level, perineural invasion, lymph node dissection (LND) number, and adjuvant EBRT were independent factors associated with OS. A risk‐stratification system was generated, which showed that low‐risk patients had a higher 5-year survival rate than high-risk patients (75.6% vs. 42.3%, p < 0.001). Adjuvant EBRT significantly prolonged the 5-year survival rate of high-risk patients (62.6% vs. 38.3%, p = 0.009) but showed no survival benefit among low‐risk patients (87.7% vs. 73.2%, p = 0.100). Our risk‐stratification model comprising age, serum CEA, perineural invasion, and LND number predicted the outcomes of patients with stage pT4b sigmoid colon cancer based on which subgroup of high-risk patients should receive adjuvant EBRT.

Efficacy of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy.

9578 Background: Adjuvant (adj) radiotherapy (RT) halves the risk of locoregional (LR) recurrence in patients (pts) with high risk stage III melanoma after lymphadenectomy (CLND), however its role in the adj immunotherapy (IO) era without CLND is unknown. Methods: Pts with resected stage III melanoma who received adj IO and recurred with resectable LR only disease were studied. After resection of this 1st recurrence, adj RT may or may not have been administered. Disease characteristics, treatment at relapse and outcomes were examined. Results: 71 pts from 9 centres were included. Prior to adj IO, median age was 60y, 59% male, 56% BRAF mutant, 61% stage IIIC (AJCC V8), 52% underwent CLND and 17% had in-transit (IT) only disease. Adj IO included: 90% single agent anti-PD1, 8% ipilimumab-nivolumab (IN) and 1% nivolumab or IN (blinded on trial). Median duration of adj IO was 5 months. 21(30%) pts had high risk stage III disease at diagnosis, per previously established TROG criteria; 3 (4%) received upfront adj RT prior to recurrence. Median time to 1st recurrence was 7 months. 49 (69%) pts recurred during and 22 (31%) after cessation of adj IO. At 1st recurrence, 9 (13%) pts had stage IIIB disease, 55 (77%) IIIC, 7 (10%) IIID and 8 (11%) continued prior adj IO, 31 (44%) commenced therapy and 32 (45%) had no systemic therapy. 24 (34%) pts received adj RT after resection of 1st recurrence and 47 (66%) did not (Table). Adj RT was associated with a reduced risk of any 2nd recurrence (7/24, 29% vs 26/47, 55%, p=0.03) and LR 2nd recurrence (2/24, 8% vs 17/47, 36%, p=0.012). Whilst pts who received adj RT at 1st recurrence were more likely to have LN only disease, extra nodal extension and involved surgical margins, these factors did not significantly affect overall risk of 2nd recurrence on multivariate analysis. Of note, 70% of pts who did not receive adj RT at 1st recurrence had IT only disease, and though this did not significantly affect rate of 2nd recurrence (p=0.19), this likely reflects an inherent selection bias in this study. RT toxicity occurred in 16 (67%) pts, 10 with dermatitis only, and all grade 1 or 2. Median follow up was 22 months. Median recurrence free survival to 2nd recurrence was 23 months for all pts, not reached for those who had adj RT at 1st recurrence and 19 months for those who did not have adj RT (p=0.047). Median overall survival was not reached. Conclusions: Whilst adj RT appears to reduce 2nd recurrences, this may have been influenced by an unavoidable selection bias in the data, particularly an imbalance in the percentage of pts with IT disease. Prospective data with larger cohorts is needed to validate our results.[Table: see text]

Necrosis and Brain Invasion Predict Radio-Resistance and Tumor Recurrence in Atypical Meningioma: A Retrospective Cohort Study.

Meningiomas are the most common tumors occurring in the central nervous system, with variable recurrence rates depending on World Health Organization grading. Atypical (Grade II) meningioma has a higher rate of recurrence than benign (Grade I) meningioma. The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned. To investigate clinical and histopathological predictors of tumor recurrence and radio-resistance in atypical meningiomas. This cohort study retrospectively reviewed all patients in St. Michael's Hospital CNS tumor patient database who underwent surgical resection of a Grade II meningioma from 1995 to 2015. Cases with neurofibromatosis type II, multiple satellite tumors, spinal cord meningioma, radiation-induced meningioma, and perioperative death were excluded. Patient demographics, neuropathological diagnosis, tumor location, extent of resection, radiation therapy, and time to recurrence or progression were recorded. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance. Among 181 patients, the combination of necrosis and brain invasion was associated with an increased recurrence risk (hazard ratio [HR]=4.560, P=.001) and the lowest progression-free survival (PFS) relative to other pathological predictors. This trend was maintained after gross total resection (GTR, P=.001). RT was associated with decreased PFS (P=.001), even in patients who received GTR (P=.001). The combination of necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in meningioma, regardless of EOR or adjuvant RT. Our findings question the sensibility of brain invasion as an absolute criterion for Grade II status.

NCOG-49. COMBINED NECROSIS AND BRAIN INVASION PREDICT RADIO-RESISTANCE AND TUMOR RECURRENCE IN ATYPICAL MENINGIOMA

Abstract BACKGROUND Meningiomas are the most common tumors in the central nervous system, with variable recurrence rates depending on WHO grading. Atypical (WHO grade II) meningioma has a higher recurrence rate than benign meningioma (WHO grade I). The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned. METHODS This cohort study retrospectively reviewed all patients at St. Michaels Hospital Tumor Patient Database with a diagnosis of atypical meningioma (AM) who underwent surgical resection between 1995 and 2015. Patient and tumor characteristics such as location, neuropathological diagnosis, resection extent, RT and time to reoccurrence or progression were recorded. Resection extent was defined by Simpson Grading Scale as either Gross Total (GTR) or Subtotal (STR) resection. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance. RESULTS In our cohort of 181 patients, the combination of necrosis and brain invasion was associated with an increased reoccurrence risk (HR= 4.560, P=0.001) and the lowest progression-free survival relative to other histopathological predictors. This trend was maintained after GTR (P=0.001), whereas necrosis alone and combined necrosis and brain invasion were both associated with low progression-free survival in STR (P=0.001). Radiotherapy was associated with decreased progression-free survival (P=0.001), especially in patients who received GTR (P=0.001). This trend was maintained in patients with necrosis alone (P=0.002) but especially in patients with combined necrosis and brain invasion (P=0.001). CONCLUSION Combined necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in AM, regardless of extent of resection or RT.

Efficacy of Adjuvant Radiotherapy for High-grade Dedifferentiated Liposarcoma in Elderly Patients

Efficacy of Adjuvant Radiotherapy for High-grade Dedifferentiated Liposarcoma in Elderly Patients

Adjuvant radiotherapy following radical prostatectomy for prostate cancer: A systematic review and meta-analysis.

366 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing efficacy of adjuvant radiotherapy (AR) versus expectant management (EM) in men who undergo radical prostatectomy for localized prostate cancer (CaP). Methods: To perform this review and meta-analysis,several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included all the studies that compared AR versus EM after radical surgery for CaP. The primary endpoints analyzed were biochemical progression-free survival (bPFS), metastasis-free survival (MPFS), prostate cancer-specific survival (CSS), overall survival (OS) and side effects. The data extracted from the studies were combined by using the Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 68 studies were identified and screened. The final analysis included 7 trials (EORTC 22911, SWOG 8794, ARO 96-02/AUO AP 09/95, RAVES, FINNISH, GETUG-AFU 17 and RADICALS-RT) comprising 4,221 patients. The bPFS was higher in patients who received AR (fixed effect: HR = 0.58, CI95% = 0.52 to 0.66; p &lt; 0.00001) but with significant heterogeneity (Chi2 = 40.34, df = 6 (P &lt; 0.00001); I2 = 85%). We performed a random-effect model analysis to better explore this heterogeneity: in this analysis, the result remained in favor of AR (random effect: HR = 0.64, CI95% = 0.45 to 0.90; p = 0.01). The MPFS also was higher in patients who received AR (HR = 0.77, CI95% = 0.65 to 0.91; p = 0.002). The CSS and OS were not statistically different in patients with or without adjuvant radiotherapy (HR = 0.79, CI95% = 0.47 to 1.32; p = 0.36 and HR = 0.92, CI95% = 0.77 to 1.11; p = 0.38, respectively). The incidence of adverse events (gastrointestinal and genitourinary) were higher in the AR group. Conclusions: This is the first meta-analysis including the seven available RCTs in the literature (the previous meta-analysis reviewed only three), comparing adjuvant radiotherapy versus expectant management following radical prostatectomy for CaP. Adjuvant radiotherapy statistically increased the bPFS and MPFS, but did not have an impact on the OS or CSS.

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy: A 10-year real-world evidence.

ObjectiveA prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy.MethodsPatients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients’ outcome, adverse events, long-term recurrence and survival rates were investigated.ResultsThe 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05).ConclusionsOur updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma.

Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post-subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post-subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

Analysis of isolated loco-regional recurrence rate in intermediate risk early cervical cancer after a type C2 radical hysterectomy without adjuvant radiotherapy.

The efficacy of adjuvant radiotherapy in patients with intermediate risk early cervical cancer after radical hysterectomy is still under debate. Most guidelines recommend adjuvant radiotherapy, whereas others consider observation a viable option. To investigate if patients with intermediate risk factors for cervical cancer who underwent radical hysterectomy may benefit from adjuvant radiotherapy. Consecutive patients with tumor confined to the cervix and intermediate risk factors (according to Sedlis), treated between January 1982 and December 2014 who were observed after a type C2 radical hysterectomy formed the basis for this study. The frequency of recurrences, specifically isolated loco-regional recurrences, and the risk of death from recurrences, were analyzed. Data were analyzed using SPSS, version 23.0 for Windows RESULTS: A total of 161 patients were included in the analysis. Median age was 40 (range 20-76). Stages IB1 and IB2 were seen in 87 (54%) and 74 patients (46%), respectively. Squamous cell and non-squamous histology was seen in 114 (70.8%) and 47 patients (29.2%), respectively. Of the 161 patients, 25 (15.5%) had recurrent disease, of whom nine had an isolated loco-regional recurrence (5.6%). Median time to recurrence for isolated loco-regional recurrences was 28 months (range 9-151). Treatment for an isolated loco-regional recurrence was radiotherapy (n = 4) and chemoradiotherapy (n = 5). Four patients (2.5%) died from disease as a result of an isolated loco-regional recurrence. Actuarial disease- specific survival was 93.0% for the total group. No variables were found that predicted an isolated loco-regional recurrence. The mortality from isolated loco-regional recurrence in patients with intermediate risk factors for cervical cancer who underwent only radical hysterectomy type C2 was 2.5%. Further studies should compare outcomes between patients who undergo a type C2 radical hysterectomy without adjuvant radiotherapy with those undergoing a less radical hysterectomy but with adjuvant radiotherapy.

Efficacy of adjuvant radiotherapy in non-extremity soft tissue sarcoma with moderate chemosensitivity.

PurposeSoft tissue sarcoma (STS) is a rare and heterogeneous cancer with over 50 known subtypes. It is difficult to understand the role of adjuvant treatment in STS. We aimed to determine the benefits of adjuvant treatment for a rare STS subset: non-extremity STS with moderate chemosensitivity.Materials and MethodsWe reviewed medical records from Pusan National University Hospital and Kosin University Gospel Hospital, which had detailed pathological reports on patients diagnosed between 2006 and 2016. The most important inclusion criterion was resection with curative intent. We grouped STS by chemosensitivity based on reported data and analyzed non-extremity STS with moderate chemosensitivity.ResultsWe investigated 142 patients with 20 pathological subtypes of STS. Eighty-six patients had extremity STS and 56 had non-extremity STS. Thirty-eight of 56 patients were categorized as having moderate chemosensitivity. Seventeen of 38 patients (44.7%) received adjuvant radiotherapy and 14 (36.8%) received adjuvant chemotherapy. A log-rank test showed longer disease-free survival (DFS) in the adjuvant radiotherapy group than in the group treated without adjuvant radiotherapy (not reached vs. 1.468 years, p = 0.037). Multivariate Cox proportional hazard analysis, with covariates including age, stage, resection margin, adjuvant chemotherapy, and adjuvant radiotherapy, revealed that adjuvant radiotherapy was associated with longer DFS (odds ratio = 0.369, p = 0.045). Overall survival was not correlated with adjuvant radiotherapy.ConclusionAdjuvant radiotherapy may be associated with longer DFS in patients with non-extremity STS with moderate chemosensitivity.

Prognostic Factors and Local Recurrence Pattern in Breast Phyllodes Tumors: A Nomogram Based on Retrospective Cohort Study of 404 Cases

This study investigate the effect of clinico-pathologic features, surgical approaches, and adjuvant radiotherapy on prognosis and to explore independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. The relationship of clinico-pathologic features, surgical treatment, and adjuvant radiotherapy with prognosis was analyzed. According to their histological type, benign PTBs were classified as a low-risk group while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups and a nomogram was made to predict recurrence-free survival at 1, 3 and 5 years. Of the 404 patients, 168 (41.6%) had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including 6 benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group while surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, patients received simple excision and with infiltrative tumor border have a higher recurrence rate. A nomogram developed based on clinico-pathologic features and surgical approaches could predict recurrence-free survival at 1, 3 and 5 years. Histological grade and degree of stromal malignancy were closely associated with postoperative local recurrence of PTB. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, and degree of stromal cell hyperplasia and atypia can be applied for patient counselling and clinical management. The efficacy of adjuvant radiotherapy is still uncertain.

Tailoring Adjuvant Radiotherapy in Endometrial Cancer

The aim of this study was to examine the patterns of failure following adjuvant radiotherapy in patients with endometrial cancer according to: (a) the extent of the disease present at the time of primary surgery, (b) according to risk groups as agreed upon in the ESMO–ESGO–ESTRO consensus conference on endometrial cancer (Colombo et al. in Int J Gynecol Cancer Off J Int Gynecol Cancer Soc 26:2–30, 2016). One thousand two hundred and seven newly diagnosed endometrial cancer patients with endometrioid/serous, clear cell and serous histology, treated by primary surgery and presented to The Peter MacCallum Cancer Centre, between January 1996 and December 2014 for adjuvant radiotherapy, were analysed for patterns of any failure to study the efficacy of adjuvant radiotherapy. Nine hundred and eight (75%) patients were alive at the last observation date, 826 without any evidence of disease. Two hundred and sixty-one patients have died, 147 (12%) from recurrent cancer. The median follow-up time was 5.4 years. 53% patients had LVSI, and 18% patients had positive nodes. 19% patients developed metastases. Pelvic, para-aortic and distant relapses were observed in 13, 11 and 8.5%, respectively. Vaginal vault brachytherapy was a very efficient form of radiotherapy that provided 99% control of disease at the vaginal vault in intermediate- and high-intermediate-risk patients in FIGO stages 1 and 2. In stage 3 and 4 patient, adjuvant pelvic radiotherapy and extended field radiotherapy provided a good pelvic and para-aortic control. Patients with lymphovascular space invasion recur more diffusely and at multi-sites.

The efficacy of adjuvant radiotherapy in dermatofibrosarcoma protuberans: a systemic review and meta‐analysis

Dermatofibrosarcoma protuberans (DFSP) is a rare and locally aggressive tumour, with a high recurrence rate, even after complete surgical excision. Adjuvant radiotherapy (RT) has been suggested to reduce the risk of local recurrence after inadequate surgical resection in patients with narrow or positive surgical margins. However, the overall efficacy of adjuvant RT has not been well studied because of the rarity of DFSP and lack of an appropriate comparison group. We sought to evaluate the efficacy of adjuvant RT for DFSP by conducting a systemic review and meta-analysis to provide a more evidence-based measure of its effectiveness. We conducted a systemic review of articles published before 31 June 2015. Due to the rarity of the disease, we included all studies that reported DFSP patients who received adjuvant RT (postoperatively). The pooled recurrence rates were analysed from these extracted data. Twelve studies met the inclusion criteria. The pooled estimate of the recurrence rate for all adjuvant radiotherapy was 11.74% (95% CI 7.4-17.38; n=167). Patients with positive/close had a pooled recurrence rate of 14.23% (95% CI 8.13-22.49; n=92), whereas there was no recurrence in patients with negative margins. The pooled estimate of the recurrence rate between surgery alone and surgery combined with adjuvant radiotherapy showed no significant difference (odds ratio 0.31, P=0.07), although there was a trend that adjuvant RT had a lower recurrence rate than surgery alone. Adjuvant RT might be considered for all patients undergoing surgical excision, even if a negative surgical margin has been achieved. Furthermore, for patients with large or recurrent tumours, especially when wide excision with negative margin would result in a significant functional or cosmetic deficit, postoperative radiotherapy is highly recommended in order to achieve a lower recurrence rate.

Radiation Therapy Significantly Improves Survival Of Patients With Diffuse Large B-Cell Lymphoma Associated With MYC Translocation: A Report From The International DLBCL Rituximab-CHOP Consortium Program

▪ Context and objectiveApproximately 5-10% of diffuse large B-cell lymphoma (DLBCL) patients carry MYC gene translocations (MYC-translocation+) with a poor prognosis after standard chemotherapy. MYC-translocation+ DLBCL patients carrying BCL2 translocations (MYC+/BCL2+ double-hit lymphoma) have a worse survival. The efficacy of adjuvant radiotherapy in this setting is unknown. The purpose of this study is to evaluate the efficacy of radiotherapy as a part of the therapeutic regimen for patients with MYC-translocation+ DLBCL. Patients and methodsFrom the International DLBCL R-CHOP consortium program, we selected 581 patients with de novo DLBCL treated with standard R-CHOP immunochemotherapy (diagnosed and treated from 2000 to 2010). We excluded patients with transformed DLBCL, primary mediastinal, cutaneous, testicular or central nervous system large B-cell lymphomas, patients with HIV infection, and patients not treated with R-CHOP. The median follow-up was 54.9 months. Fluorescence in situ hybridization assessing MYC was performed for all the patients (n=581) and results were correlated with available clinical data to identify clinicopathologic features associated with MYC translocation, and to evaluate the prognostic significance of MYC translocations regarding overall survival (OS, from the time of diagnosis to death from any cause) and progression-free survival (PFS, from the time of diagnosis to relapse or death from any cause). In the MYC-translocation+ DLBCL group, 38 patients received chemotherapy alone and 21 patients received chemotherapy with adjuvant radiation therapy. The clinicopathologic features and survival of MYC-translocation+ DLBCL patients treated with (n=21) and without radiotherapy (n=38) after immunochemotherapy were compared to in order to evaluate the radiotherapy efficacy and other confounding factors. ResultsMYC translocations were detected in 59 DLBCL patients (10.2%). Patients with MYC-translocation+ DLBCL more often had bulky tumors, involvement of multiple extranodal sites, and poorer OS (hazard ratio [HR]: 2.0, 95% confidence interval [CI]: 1.20 - 3.35, P= .0083) and PFS (HR: 1.96, 95% CI: 1.22 - 3.13, P= .0005) independent of the International Prognostic Index score. Poor survival was primarily attributable to patients with MYC+/BCL2+ double-hit DLBCL who were predominantly of germinal center B-cell subtype. Among MYC-translocation+ DLBCL patients, a better survival was achieved in patients who received radiotherapy (for OS, HR: .32, 95% CI: .15 - .71, P= .0049; for PFS, HR: .35, 95% CI: .17 - .73, P= .0043). Conversely, radiotherapy abolished the adverse impact of MYC translocations. In addition, radiotherapy was associated with better survival in the subset of patients with MYC+/BCL2+ double-hit lymphoma (P = .017 for OS, and P = .05 for PFS). However, owing to the common use of radiotherapy as consolidation therapy, the favorable prognoses in the group of patients who received radiotherapy could also be attributed to limited-stage disease and more frequent complete remission (CR) after first-line treatment and therefore these factors confound interpretation of the data. To address these issues, we evaluated radiotherapy efficacy in separate patient groups: patients who achieved CR, non-CR (PR/SD/PD) patients, and patient with stage I/II, or stage III/IV disease. The efficacy of radiotherapy appeared more apparent in patients with advanced disease who did not achieve CR after first-line chemotherapy. Multivariate analysis after adjustment for stage and IPI score validated that radiotherapy significantly improved OS (HR: .28, 95% CI: .10 - .81, P= .018) and PFS (HR: .32, 95% CI: .13 - .80, P= .015) of MYC-translocation+ DLBCL patients. ConclusionsThe presence of MYC translocations in DLBCL is an important biomarker that facilitates prognostic prediction and treatment stratification independent of the IPI score. For chemoresistant MYC-translocation+ DLBCL patients, radiotherapy seems to be an effective adjuvant regimen likely due to the higher frequency of extranodal involvement and bulky disease in MYC-translocation+ DLBCL patients. Our results provide a rationale for larger scale studies to assess the potential role of radiotherapy in the management of MYC-translocation+ DLBCL patients, particularly patients with MYC+/BCL2+double-hit DLBCL. Disclosures:Winter:Millenium: Research Funding; Novartis : Research Funding; Pfizer (Wyeth): Research Funding; Seattle Genetics: Research Funding; Spectrum: Research Funding; Janssen (Pharmacyclics): Research Funding; Spectrum (Allos): Consultancy; Sanofi Aventis: Consultancy; Tgen: Consultancy; AMBIT Biosciences (Spouse): Research Funding; Celgene (Spouse): DSMB, DSMB Other, Research Funding; Ariad Pharmaceuticals (Spouse): Research Funding; Novartis (Spouse): Consultancy, Research Funding; Amgen (Spouse): Consultancy, Research Funding; Astellas (Spouse): Research Funding; Caremark/CVS: Consultancy; Pfizer (Spouse): Consultancy; Sanofi Aventis (Spouse): DSMB, DSMB Other; Bristol Myers Squibb (Spouse): DSMB, DSMB Other; UptoDate, Inc.(Spouse): Patents & Royalties.

Radiation Therapy Significantly Improves Survival Of Patients With Diffuse Large B-Cell Lymphoma Associated With MYC Translocation: A Report From The International DLBCL Rituximab-CHOP Consortium Program

▪ Context and objectiveApproximately 5-10% of diffuse large B-cell lymphoma (DLBCL) patients carry MYC gene translocations (MYC-translocation+) with a poor prognosis after standard chemotherapy. MYC-translocation+ DLBCL patients carrying BCL2 translocations (MYC+/BCL2+ double-hit lymphoma) have a worse survival. The efficacy of adjuvant radiotherapy in this setting is unknown. The purpose of this study is to evaluate the efficacy of radiotherapy as a part of the therapeutic regimen for patients with MYC-translocation+ DLBCL. Patients and methodsFrom the International DLBCL R-CHOP consortium program, we selected 581 patients with de novo DLBCL treated with standard R-CHOP immunochemotherapy (diagnosed and treated from 2000 to 2010). We excluded patients with transformed DLBCL, primary mediastinal, cutaneous, testicular or central nervous system large B-cell lymphomas, patients with HIV infection, and patients not treated with R-CHOP. The median follow-up was 54.9 months. Fluorescence in situ hybridization assessing MYC was performed for all the patients (n=581) and results were correlated with available clinical data to identify clinicopathologic features associated with MYC translocation, and to evaluate the prognostic significance of MYC translocations regarding overall survival (OS, from the time of diagnosis to death from any cause) and progression-free survival (PFS, from the time of diagnosis to relapse or death from any cause). In the MYC-translocation+ DLBCL group, 38 patients received chemotherapy alone and 21 patients received chemotherapy with adjuvant radiation therapy. The clinicopathologic features and survival of MYC-translocation+ DLBCL patients treated with (n=21) and without radiotherapy (n=38) after immunochemotherapy were compared to in order to evaluate the radiotherapy efficacy and other confounding factors. ResultsMYC translocations were detected in 59 DLBCL patients (10.2%). Patients with MYC-translocation+ DLBCL more often had bulky tumors, involvement of multiple extranodal sites, and poorer OS (hazard ratio [HR]: 2.0, 95% confidence interval [CI]: 1.20 - 3.35, P= .0083) and PFS (HR: 1.96, 95% CI: 1.22 - 3.13, P= .0005) independent of the International Prognostic Index score. Poor survival was primarily attributable to patients with MYC+/BCL2+ double-hit DLBCL who were predominantly of germinal center B-cell subtype. Among MYC-translocation+ DLBCL patients, a better survival was achieved in patients who received radiotherapy (for OS, HR: .32, 95% CI: .15 - .71, P= .0049; for PFS, HR: .35, 95% CI: .17 - .73, P= .0043). Conversely, radiotherapy abolished the adverse impact of MYC translocations. In addition, radiotherapy was associated with better survival in the subset of patients with MYC+/BCL2+ double-hit lymphoma (P = .017 for OS, and P = .05 for PFS). However, owing to the common use of radiotherapy as consolidation therapy, the favorable prognoses in the group of patients who received radiotherapy could also be attributed to limited-stage disease and more frequent complete remission (CR) after first-line treatment and therefore these factors confound interpretation of the data. To address these issues, we evaluated radiotherapy efficacy in separate patient groups: patients who achieved CR, non-CR (PR/SD/PD) patients, and patient with stage I/II, or stage III/IV disease. The efficacy of radiotherapy appeared more apparent in patients with advanced disease who did not achieve CR after first-line chemotherapy. Multivariate analysis after adjustment for stage and IPI score validated that radiotherapy significantly improved OS (HR: .28, 95% CI: .10 - .81, P= .018) and PFS (HR: .32, 95% CI: .13 - .80, P= .015) of MYC-translocation+ DLBCL patients. ConclusionsThe presence of MYC translocations in DLBCL is an important biomarker that facilitates prognostic prediction and treatment stratification independent of the IPI score. For chemoresistant MYC-translocation+ DLBCL patients, radiotherapy seems to be an effective adjuvant regimen likely due to the higher frequency of extranodal involvement and bulky disease in MYC-translocation+ DLBCL patients. Our results provide a rationale for larger scale studies to assess the potential role of radiotherapy in the management of MYC-translocation+ DLBCL patients, particularly patients with MYC+/BCL2+double-hit DLBCL. Disclosures:Winter:Millenium: Research Funding; Novartis : Research Funding; Pfizer (Wyeth): Research Funding; Seattle Genetics: Research Funding; Spectrum: Research Funding; Janssen (Pharmacyclics): Research Funding; Spectrum (Allos): Consultancy; Sanofi Aventis: Consultancy; Tgen: Consultancy; AMBIT Biosciences (Spouse): Research Funding; Celgene (Spouse): DSMB, DSMB Other, Research Funding; Ariad Pharmaceuticals (Spouse): Research Funding; Novartis (Spouse): Consultancy, Research Funding; Amgen (Spouse): Consultancy, Research Funding; Astellas (Spouse): Research Funding; Caremark/CVS: Consultancy; Pfizer (Spouse): Consultancy; Sanofi Aventis (Spouse): DSMB, DSMB Other; Bristol Myers Squibb (Spouse): DSMB, DSMB Other; UptoDate, Inc.(Spouse): Patents & Royalties.

Feasibility of 6 months of maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck (HNC).

e16033 Background: The prognosis for HNC patients (pts) after surgical treatment and adjuvant chemoradiation (CRT) is unsatisfactory in case of close resection margin &lt;5 mm (CM) or extra capsular extent at the lymph nodes (ECE). Therefore we conducted a multicenter phase II study to investigate the toxicity and efficacy of adjuvant radiotherapy (RT) in combination with concurrent cisplatin, 5- fluorouracil (5FU), and cetuximab (CTX) followed by maintenance therapy with CTX for 6 months. Here, we present the preliminary results on feasibility and toxicity. Methods: HNC pts after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin [20 mg/m2 d1-5 and d29-33] and 5-FU (CI 600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative RT using an integrated boost IMRT-technique (1.8/2.0/2.2Gy QD) to a total dose of 61.6 Gy. CTX started 7 days prior CRT with a loading dose of 400 mg/m2 followed by weekly CTX (250 mg/m2) during CRT. Maintenance CTX started after completion of CRT plus CTX with 500 mg/m² every 2 weeks over a 6-month period. Results: 55 of 80 planned pts (46 male, 9 female, mean age 55.6, range 29-70 years) have finished CRT, 50 are evaluable for toxicity. Concurrent CRT plus CTX was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reaction outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). CTX was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts CTX was discontinued during the last 2 weeks or at the end of CRT. Of those pts embarking on maintenance therapy, 80% were still on CTX after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant CRT in combination with CTX followed by maintenance CTX is feasible with toxicity in the expected range. Compliance to maintenance CTX was satisfactory during the first 3-5 months.

Glioblastoma in elderly patients: Safety and efficacy of adjuvant radiotherapy with concomitant temozolomide

The aim of this study was to evaluate the impact of radiotherapy plus concomitant and adjuvant temozolomide (TMZ), in terms of feasibility and activity, in elderly patients with glioblastoma. From January 2002 to December 2007, 42 consecutive patients with glioblastoma (27 men and 15 women) aged 65 years or more (median age 71.3 years), received radiotherapy plus concomitant and adjuvant TMZ. Nineteen patients (45.2%) had a Karnofsky index ≥80. Thirty-six patients (85.8%) underwent complete or subtotal resection, while 6 patients (14.2%) were only biopsied. All patients received adjuvant radiotherapy within 4 weeks from surgery. Twenty-two patients (54.8%) underwent adjuvant TMZ. Early discontinuation of concomitant TMZ program due to toxicity was observed in 8 patients. Considered variables were: age, Karnofsky index, surgery versus no surgery, radiation dose, and chemotherapy. At a median follow-up of 10.2 months, the 6- and 12-month overall survival rates were 81.9% and 27.8%, respectively. There was a significantly better survival for patients with a performance status according to Karnofsky >80 ( p < 0.0001). Actuarial progression-free survival at 6- and 12-month was 46.4% and 9.8%, respectively. Globally, the treatment was well tolerated with no treatment-related toxicity in 69% of patients. In conclusion, in elderly patients, the adjuvant chemo-radiotherapy was well tolerated with an acceptable rate of toxicity, and patients with a good performance status had a significantly better survival. However, further prospective trials are needed to confirm these results.

Cutaneous head and neck squamous cell carcinoma metastatic to parotid and cervical lymph nodes

Nonmelanoma skin cancers occur at an epidemic rate in Australia and are increasing in incidence worldwide. In most patients, local treatment is curative. However, a subset of patients will be diagnosed with a high-risk cutaneous squamous cell carcinoma (SCC) and are defined as patients at increased risk of developing metastases to regional lymph nodes. Patients with high-risk SCC may be identified based on primary lesion and patient factors. Most cutaneous SCC arises on the sun-exposed head and neck. The parotid and upper cervical nodes are common sites for the development of metastases arising from ear, anterior scalp, temple/forehead, or scalp SCC. The mortality and morbidity associated with high-risk cutaneous SCC is usually a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Patients with operable nodal disease have traditionally been recommended for surgery. The efficacy of adjuvant radiotherapy has previously been questioned based on weak evidence in the early literature. Recent evidence from larger studies has, however, strengthened the case for adjuvant radiotherapy as a means to improve locoregional control and survival. Despite this, many patients still experience relapse and die. Research aimed at improving outcome such as a randomized trial incorporating the addition of chemotherapy to adjuvant radiotherapy is currently in progress in Australia and New Zealand. Ongoing research also includes the development of a proposed new staging system and investigating the role of molecular factors such as the epidermal growth factor receptor.