Local-regional Failure-free Survival Research Articles

Prognostic value of Epstein-Barr virus DNA load in nasopharyngeal carcinoma: a meta-analysis.

The present meta-analysis was conducted to evaluate the prognostic value of pre and post-Epstein Barr Virus (EBV) DNA load testing and to assess the clinical benefit of using this molecular approach in the prognosis for a better nasopharyngeal carcinoma (NPC) management. Relevant studies were searched in different database until May 2020. Patient´s outcomes overall survival (OS), disease free survival (DFS), progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS), hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies. The association of pre and post-EBV DNA load and survival outcomes was assessed using review manager and the pooled HRs with 95% CIs were calculated. Twenty-six eligible studies were included in this meta-analysis, with a total of 9966 patients. Pooled HRs showed that EBV DNA levels before and after treatment are significantly associated with survival outcomes, with HR (95% CI) of 2.09 [1.74, 2.51] for OS, 1.77 [1.19, 2.62] for DFS, 2.53 [2.18, 2.92] for DMFS, 1.78 [1.45, 2.19] for LRFS and 2.17 [1.91, 2.47] for PFS in pre-EBV DNA, and an HR (95%) of 4.52 [2.44, 8.36], 4.08 [2.38, 6.99], 5.59 [ 3.58, 8.71] and 8.88 [5.29, 14.90] for OS, DFS and PFS and DMFS in post-EBV DNA, respectively. High pre and post-EBV DNA levels were significantly associated with poor NPC patient´s survival outcomes; which clearly confirm the high interest to introduce viral EBV DNA load as a prognostic biomarker for NPC management.

Clinical outcomes of different irradiation ranges in definitive intensity-modulated radiotherapy for esophageal cancer

Objective: To explore the therapeutic efficacy and safety of elective nodal irradiation (ENI) and involved field irradiation (IFI) in intensity-modulated radiotherapy for esophageal cancer, screen the patients suitable to undergo ENI radiotherapy and provide evidences for individual treatment of esophageal cancer. Methods: A retrospective analysis was performed on the clinical data of 924 patients with esophageal cancer who received definitive intensity-modulated radiotherapy in our hospital from January 2006 to December 2015. Among them, 272 patients received ENI and the other 652 patients received IFI. The clinicopathologic characteristics of 272 cases in ENI group and 652 cases in IFI group, who were recruited according to the balance of propensity score matching method, were compared. The Kaplan-Meier method was used to calculate 1-year, 3-years and 5-years local-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS) rates. The univariate and multivariate analysis of prognostic factors were also determined by Cox proportional hazard model and Long-rank test. Results: The clinicopathologic characteristics of these two group were not significantly different (P>0.05). The median follow-up time was 85.9 months and the follow-up rate was 95.9%. The 1-year, 3-years, 5-years PFS rates of the ENI groups were 65.3%, 31.7%, 18.4%, respectively, higher than 54.0%, 20.9%, 12.7% of the IFI group (P=0.001). The 1-year, 3-years, 5-years OS rates of the ENI groups were 79.0%, 43.7%, 24.9%, respectively, higher than 75.0%, 31.8%, 17.2% of the IFI group (P=0.003). In multivariate analysis, the sex, tumor volume, N stage and radiation field were independent factors for PFS and OS (P<0.05). Subgroup analysis showed that patients with male, age≤66 year, cervical and upper-thoracic location, tumor length≤6 cm, T1-2 stage, N0-1 stage, Ⅰ-Ⅱ stage, tumor volume≤50 cm(3), dosage>60 Gy and≤2 cycles of chemotherapy in the ENI group had a better survival rate than those in the IFI group (P<0.05). The total failure rate, local-regional failure rate in ENI group were significantly lower than those of IFI group (P=0.001, P=0.004). The incidence of bone marrow depression≥ grade 2 and 3 in ENI group was higher than that of the IFI group (P<0.05). However, the incidences of radioactive esophagitis≥ grade 3, radioactive pneumonia and late adverse reactions were not significantly different between these two groups (P>0.05). Conclusion: Compared with IFI, ENI can significantly improve the long-term survival for young, early TN stage and cervical/upper-thoracic esophageal cancer patients underwent chemotherapy.

Real-World Analysis of Clinical Characters, Prognosis, And Recurrence Pattern: A Retrospective Multicenter Study of 429 Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Advanced NSCLC with EGFR mutations is a distinct subgroup which has unique biology and a high response rate towards target therapy of EGFR-tyrosine kinase inhibitors (TKIs). However, for EGFR-mutant unresectable LA-NSCLC who treated with conventional chemoradiotherapy (CRT), limited data are available about the relationship between clinical characteristics, prognosis, and subsequent failure patterns. Here we summarized these clinical data using a joint academic center database. We retrospectively collected data for patients with unresectable stage III NSCLC harboring EGFR mutations from nine major academic cancer institutions in China from Jan 2012 to December 2018. Patients with concurrent ALK rearrangements were excluded. Tumor or ctDNA genotyping was performed using polymerase chain reaction amplification or next-generation sequencing method. OS, PFS, local-regional failure free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated from the date of diagnosis. A total of 429 patients met selection criteria were included in the study, among whom 209 (48.7%) patients had exon 19 deletion, 165 (38.5%) had L858R exon, 26 (6.1%) had uncommon mutations, and 29 (6.8%) had multiple mutations. 298 patients (69.5%) were smoker, and 227 (61.9%) were female. The median age was 58 (30-89) years and 230 (53.6%) was younger than 60 years. 296 (69.0%) patients had stage IIIB disease and 285patients (66.4%) with smaller primary lesions (T1/2). Of the 367 patients with survival information, the median follow-up time was 40.8 months. the median OS were 55.5 month (95%CI 43.4-67.5). The 1-, 2-, 3-, and 5-years OS rates are 94%, 79%, 63%, and 47%, respectively. The median PFS was 16.6 months (95%CI 14.9-18.2). The 1-, 2-, 3-, and 5-years PFS rates are 64%, 34%, 22%, and 14%, respectively. There was no difference in OS or PFS by different genotypes. In multivariable analysis, use of EGFR-TKIs (yes v not: HR = 0.56, 95%CI 0.43-0.74, P<0.001) and stage (IIIA v IIIB: HR = 0.67, 95% CI 0.51-0.87, P = 0.003) were independently associated with PFS; and age was independently associated with OS (≥60 v <60 years: HR = 1.45, 95% CI 1.03-2.03, P = 0.035). As for relapse pattern after initial treatment of thoracic radiotherapy (RT) and chemotherapy, 46.5% of patients developed DM, 31.0% developed LRR, and 22.5% developed simultaneous DM and LRR. The incidence of brain metastasis was 24.8% (91 patients). By multivariable analysis, EGFR-TKIs independently increased the DMFS (yes v not: HR 0.51,95%CI 0.37-0.70, P<0.001). To our knowledge this is the largest retrospective analysis of EGFR-mutant LA-NSCLC, aiming to provide a reliable baseline and prognosis estimate. Multivariable analysis demonstrated EGFR-TKIs might independently prolong DMFS. The combined treatment modality of RT and EGFR-TKIs may be promising.

A meta-analysis of cisplatin-based concurrent chemoradiotherapy with or without cetuximab for locoregionally advanced nasopharyngeal carcinoma.

Background:It is unclear whether cetuximab (CTX) plus cisplatin-based concurrent chemoradiotherapy (CCRT) delivers equivalent or improved results over standard CCRT in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods:The strategy involved searching the PubMed, Embase, Cochrane Library, and Web of Science. Pooled hazard ratios (HRs) for overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS), and pooled risk ratios for adverse events were meta-analyzed.Results:In all, 1744 patients in 5 clinical trials were included in the analysis. Compared with CCRT group, CTX plus CCRT significantly improved DFS (HR = 0.59, 95% confidence interval [CI]: 0.41–0.86, P = .006) and distant metastasis failure-free survival (HR = 0.54, 95% CI: 0.38–0.76, P = .0004), rather than OS (HR = 0.70, 95% CI: 0.44–1.09, P = .12) and local-regional failure-free survival (HR = 0.82, 95% CI: 0.54–1.22, P = .33).Conclusions:CTX plus CCRT might achieve higher DFS and DMFS with no significant difference in OS and LRFS. CTX plus CCRT group was associated with more grade 3-4 skin rash, mucositis and dermatitis. Large randomized trials were urgent to fully explore the usefulness of this treatment in the locally advanced NPC patients.

Prognostic value of TIGAR and LC3B protein expression in nasopharyngeal carcinoma

PurposeAutophagy, the process responsible for degrading cytoplasmic organelles to sustain cellular metabolism, has been associated with cancer initiation and progression. As TP53-induced glycolysis and apoptosis regulator (TIGAR) is among the important genes that can regulate autophagy, we aimed to investigate the correlation between the expression levels of TIGAR and the autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3B), as well as their association with clinical outcomes, in nasopharyngeal carcinoma (NPC) patients.MethodsWe detected the expressions of TIGAR and LC3B in 182 NPC tissue samples via immunohistochemical staining.ResultsA significant correlation between TIGAR and LC3B expressions was identified (P=0.045). Moreover, survival analysis showed that TIGAR− or LC3B+ expression was associated with improved overall survival, local regional failure-free survival, distant failure-free survival, and failure-free survival rates, compared with TIGAR+ or LC3B− expression, respectively. Meanwhile, when combining TIGAR with LC3B expression in terms of prognostic value, patients with TIGAR+/LC3B− expression were significantly disadvantaged with regard to overall survival, local regional failure-free survival, distant failure-free survival, and failure-free survival compared with other groups based on the log-rank test and Cox regression analyses (all P<0.05).ConclusionTIGAR and LC3B may be novel biomarkers for predicting the prognosis of NPC patients and could be utilized as potential targets for future therapeutics aimed at treating NPC patients.

Aging-related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer.

Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.

Cetuximab or Nimotuzumab Versus Cisplatin Concurrent with Radiotherapy for Local-Regionally Advanced Nasopharyngeal Carcinoma: a Meta-analysis

Background:It is unclear whether Cetuximab (CTX) or Nimotuzumab (NTZ) concurrent with radiotherapy delivers equivalent or improved results with fewer toxicities over standard cisplatin (CDDP) concurrent with radiotherapy in locally advanced nasopharyngeal carcinoma (NPC).Methods:The strategy involved searching the PubMed, Embase, Cochrane Library, China National Knowledge Internet Web, Wanfang and Chinese Biomedical databases. Controlled clinical trials that compared concurrent CTX/NTZ with radiotherapy versus CDDP with radiotherapy in local-regionally advanced NPC were included.Results:In all, 1,239 patients in six clinical trials were included in the analysis. The hazard ratios (HRs) between the CTX/NTZ and CDDP groups were 1.01 (95% confidence interval (CI) 0.63-1.64), 1.06 (95% CI 0.50-2.25), 1.04 (95% CI 0.61-1.76), and 1.05 (95% CI 0.73-1.50) for overall survival, local-regional failure-free survival, distant metastasis failure-free survival, and disease-free survival, respectively. Significant differences were found in the incidences of grade 3-4 anaemia [Risk ratio (RR) 0.11 95% CI 0.02-0.58], grade 3-4 neutropenia (RR 0.23 95% CI 0.12- 0.44), grade 3-4 thrombocytopenia (RR 0.31 95% CI 0.12- 0.79), and grade 3-4 vomiting (RR 0.04 95% CI 0.00-0.29) in favour of the CTX/NTZ group. However, the patients in the CTX/NTZ group experienced a higher incidence of grade 3-4 skin rash (RR 6.45 95% CI 3.84-10.84).Conclusions:Regarding the efficacy and side effects, the combination of CTX / NTZ and radiotherapy may be an alterative treatment regimen of standard CDDP concurrent with radiotherapy in local-regionally advanced NPC, especially in patients who cannot tolerate or who refuse chemotherapy.

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy

BackgroundEffective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities.MethodsA retrospective study was conducted in 245 patients diagnosed with locally recurrent T3–T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colleted and factors associated with survival and severe late toxicities were analyzed.ResultsThe 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Conclusions: Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3–T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

Patterns of failure and clinical outcomes of definitive radiotherapy for cervical esophageal cancer

PurposeBecause of the scarcity of cervical esophageal cancer (CEC), data for this disease entity is limited. We aim to evaluate the outcomes, prognostic factors and failure patterns of CEC treated by contemporary radiotherapy (RT).MethodsWe retrospectively analyzed 86 CEC patients consecutively treated between 2007 and 2015 by definitive RT with or without concurrent chemotherapy. RT was mainly delivered with Intensity Modulated Irradiation Therapy (IMRT) or Volumetric-Modulated Arc Therapy (VMAT). Statistical analyses were performed on survival, prognostic factors and failure patterns.ResultsThe median follow-up time was 19.4 months. The 3-year overall survival (OS), local regional failure free survival (LRFFS), distant metastatic free survival (DMFS), and progression free survival (PFS) were 53.6%, 57.9%, 81.5% and 41.5%, respectively. Independent predictors for poorer OS were N stage, hoarseness and recurrent laryngeal nerve lymph node (RLN) involvement, and predictors for LRFFS were N stage and EQD2 (equivalent dose in 2 Gy fraction) to gross tumor volume (GTV), with ≥ 66Gy achieving local control of 94.7%. Patients receiving elective nodal irradiation (ENI) had better nodal regional control than those receiving involved field irradiation (IFI). 31 (36%) patients had treatment failure and 15 (17.4%), 8 (9.3%) and 14 (16.2%) patients had local, regional, and distant failure, respectively. 86.7% (13/15) local failures were within GTV, and supraclavicular region (62.5%, 5/8) was the most common regional failure site. No severe toxicities were observed.ConclusionsOur results seem to indicate that good locoregional control might be achieved for CEC with adequate radiation dose and treatment planning approaches.

The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas.

ObjectiveThis retrospective study evaluated the role of adjuvant radiotherapy (AR) after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS) and overall survival (OS).Patients and methodsA study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30–50 Gray/10–25 fractions at five fractions/week). The primary end point was LRFFS, and the secondary end point was OS. Kaplan–Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS.ResultsThe median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013). The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067). Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively).ConclusionPatients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant radiation for patients with uterine sarcoma still requires further discussion.

The clinical utility of plasma Epstein-Barr virus DNA assays in nasopharyngeal carcinoma: the dawn of a new era?: a systematic review and meta-analysis of 7836 cases.

In this study, we assessed the potential of plasma Epstein–Barr virus (EBV) DNA assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma (NPC) patients and proposed a risk stratification model based on standardized EBV DNA load monitoring.We conducted a meta-analysis of 14 prospective and retrospective comparative studies (n = 7 836 patients) to evaluate the correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value of plasma EBV DNA clearance rate (t1/2), and clinical outcomes. Our primary endpoint was overall survival (OS). Our secondary endpoints were progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS).High pre-DNA, detectable mid-DNA, detectable post-DNA, and slow EBV DNA clearance rates were all significantly associated with poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58, respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS, and LRFS.Plasma EBV DNA assays are highly prognostic of long-term survival and distant metastasis in NPC patients. Based on the results of this meta-analysis, we propose a 4-grade systematic risk stratification model. Given the inherent limitations of the included studies, future well-designed randomized clinical trials are required to confirm to the findings of this analysis and to contribute to the development of individualized treatment strategies for NPC patients.

Evaluation of long-term efficacy of re-irradiation with intensity-modulated radiotherapy for locally recurrent nasopharyngeal carcinoma

Objective To retrospectively analyze the long-term survival, late adverse events, and prognostic factors in patients with locally recurrent nasopharyngeal carcinoma (NPC) after re-irradiation with intensity-modulated radiotherapy (IMRT) . Methods From 2001 to 2010, a total of 335 patients who were diagnosed with locally recurrent NPC and received re-irradiation with IMRT were included in the study. Among all the patients, 69 (20.6%) had radiotherapy complications. There were 268 male patients (80.0%) and the median age was 45.0 years (range:21-75 years). The numbers of patients in disease stages T1, T2, T3, and T4 were 41, 36, 122, and 136, respectively. The median tumor volume was 37.5 cm3, and the median prescribed dose to the target volume was 68 Gy (range:60-70 Gy). The survival rate was determined using the Kaplan-Meier method. Prognostic factors were analyzed by the Cox proportional hazard model. Results The 5-year follow-up sample size was 312 patients. The 5-year overall survival, local-regional failure-free survival, and distant failure-free survival were 34.7%, 64.2%, and 82.2%, respectively. Multivariate analysis indicated that the poor prognostic factors included age> 45 years (P=0.01) , presence of significant radiotherapy complications before IMRT (P=0.00) , tumor stages (T2-T4) (P=0.00) , tumor volume> 38 cm3 (P=0.01) , and the mean dose of gross tumor volume (GTVnx) >68Gy (P=0.01). The incidence rates of nasopharyngeal mucosa necrosis, epistaxis, radiation encephalopathy, cranial nerve injury, and trismus were 28.6%, 16.4%, 22.4%, 15.8%, and 13.7%, respectively. Conclusions Re-irradiation with IMRT is effective in controlling tumor and thus is a reasonable choice for patients with locally recurrent NPC. However, the incidence of severe adverse events is still high. Further investigation on how to maintain the balance between tumor control and normal organ protection is needed. Key words: Nasopharyngeal neoplasms, locally recurrent / intensity - modulated radiotherapy; Untoward effect; Prognosis

Re-evaluating the Optimal Radiation Dose for Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

The optimal radiation dose for treating esophageal squamous cell carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4 Gy delivered with modern techniques are beneficial in terms of tumor control, survival, and toxicity. We included 193 consecutive patients with ESCC treated with definitive concurrent chemoradiotherapy from 1998 to 2012. Patients were treated to a dose of ≤50.4 Gy (low-dose, n = 137) or greater than 50.4 Gy (high-dose, n = 56). Tumor response, local-regional control, survival, and treatment toxicity were compared between groups. High-dose group had a significantly lower local failure rate (17.9% versus 34.3%, p = 0.024) and a marginal better 5-year local-regional failure-free survival (68.7% versus 55.9%, p = 0.052) than the low-dose group. No significant differences were found between high- and low-dose groups in tumor complete response rate (p = 0.975), regional failure rate (p = 0.336), distant metastasis rate (p = 0.390), or 5-year overall survival (p = 0.617). No difference in the incidence of toxic effects was observed between the two groups except for grade 3 skin reaction (12.5% [high] versus 2.2% [low], p < 0.001) and grade greater than or equal to 3 esophageal stricture (32.1% [high] versus 18.2% [low], p = 0.037). Local tumor control might be improved by higher dose of greater than 50.4 Gy, when delivered with modern techniques and concurrent chemotherapy, at the consequence of increased toxicity without impact on overall survival.

The Role of Adjuvant Radiation in Uterine Sarcomas

To determine clinical and pathological factors significant for overall survival (OS) and local-regional failure-free survival (LRFFS) in uterine sarcoma as they relate to adjuvant radiotherapy (AR). A retrospective analysis of 3,650 patients with uterine sarcoma was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by Impac Medical Systems (Sunnyvale, CA). Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis, with or without brachytherapy. Prognostic factors were identified by multivariate analysis (MVA) using the Cox proportional hazards model. The Kaplan-Meier method was used to estimate survival, with significant differences (p < 0.05) determined using the log-rank test. The median follow-up time was 59 months, with a 5-year OS of 37%. Significant prognostic factors for OS were stage, race/ethnicity, grade, age, histology, lymph node status, and surgical treatment (p < 0.01 for all factors). Use of AR was not predictive for OS. For nonmetastatic cancer patients receiving definitive surgery (n = 2,206), the 5-year LRFFS was 87%. In this group, stage, grade, histology, and AR were prognostic for LRFFS (p < 0.05), with AR associated with improved outcome compared with surgery alone (hazard ratio = 0.4, p < 0.001). Patients with carcinosarcoma, endometrial stromal sarcoma, leiomyosarcoma, poorly differentiated tumors, and negative lymph nodes had reduced local-regional failure (LRF) with AR (log-rank, p < 0.05 for all). In the largest retrospective analysis of uterine sarcoma published thus far, AR conferred a 53% reduction in the risk of LRF at 5 years. Use of AR may have broader indications than what are currently accepted in clinical practice.

Tumor hypoxia and anemia: Impact on the efficacy of radiation therapy

The adverse effects of tumor hypoxia and anemia on the efficacy of radiation therapy have been increasingly recognized. In vitro data indicate that radiation therapy under hypoxic conditions is approximately one third as effective as that under normoxic conditions. There is accumulating clinical evidence of significantly reduced local-regional tumor control and overall survival in anemic patients receiving radiotherapy for head and neck, respiratory tract, pelvic, or genitourinary cancers. In our own study using intraarterial high-dose cisplatin and radiation therapy, we observed that pretreatment hemoglobin level was significantly predictive of complete response (CR) at primary and nodal sites, local-regional failure-free survival, and overall survival by multivariate analyses. With the general lack of success in overcoming the effects of tumor hypoxia through such measures as hyperbaric oxygen and radiosensitizing agents, the focus of clinical research has shifted to directly correcting anemia. A planned randomized trial by the Radiation Therapy Oncology Group will assess the effects of correction of anemia with epoetin alfa on local-regional tumor control and survival in anemic head and neck cancer patients receiving radiation therapy.