Distant Failure In Patients Research Articles

Prognostic factors and clinical outcomes of breast cancer patients with disease progression during neoadjuvant systemic therapy

Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them.Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies.Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis.Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.

Cisplatin-based concurrent chemoradiotherapy improved the survival of locoregionally advanced nasopharyngeal carcinoma after induction chemotherapy by reducing early treatment failure

PurposeThe aims of this study focusing on Locoregionally advanced nasopharyngeal carcinoma (LANPC) were mainly two-fold: on the one hand, to establish a cut-off value to differentiate early and late failure based on prognosis after recurrence or metastasis; and on the other hand, to investigate the duration of concurrent cisplatin benefit over follow-up time. The results of our study have the potential to guide clinical practice and follow-up.MethodsIn total, 3123 patients with stage III-IVa NPC receiving Induction chemotherapy followed by concurrent cisplatin or not were analysed. The cut-off value of treatment failure was calculated using the minimum P-value approach. Random survival forest (RSF) model was to simulate the cumulative probabilities of treatment failure (locoregional recurrence and /or distant metastasis) over-time, as well as the monthly time-specific, event-occurring probabilities, for patients at different treatment groups.ResultsBased on subsequent prognosis, early locoregional failure (ELRF) should be defined as recurrence within 14 months (P = 1.47 × 10 − 3), and early distant failure (EDF) should be defined as recurrence within 20 months (P = 1.95 × 10 − 4). A cumulative cisplatin dose (CCD) > 200 mg/m2 independently reduced the risk of EDF (hazard ratio, 0.351; 95% confidence interval (CI), 0.169–0.732; P = 0.005). Better failure-free survival (FFS) and overall survival (OS) were observed in concurrent chemotherapy settings ([0 mg/m2 vs. 1-200 mg/m2 vs. >200 mg/m2]: FFS: 70.4% vs. 74.4% vs. 82.6%, all P < 0.03; OS: 79.5% vs. 83.8% vs. 90.8%, all P < 0.01). In the monthly analysis, treatment failure mainly occurred during the first 4 years, and the risk of distant failure in patients treated with concurrent chemotherapy never exceeded that of patients without concurrent chemotherapy.ConclusionLocoregional failure that developed within 14 months and/or distant failure within 20 months had poorer subsequent survival. Concurrent chemotherapy provides a significant FFS benefit, primarily by reducing EDF, translating into a long-term OS benefit.

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

Metastatic disease is a significant cause of morbidity and mortality among patients with cancer. Patients with oligometastatic cancer represent a subset of the metastatic population with a limited amount of disease that has metastasized distantly and progresses at a slow pace and thus has the potential to be cured with metastasis-directed local therapy. Recent studies examining the role of metastasis-directed therapy in patients with oligometastatic disease have primarily focused upon treatment with ablative doses of radiation, commonly referred to as stereotactic body radiation therapy (SBRT). While the use of SBRT to treat oligometastases has increased considerably in recent years, the benefit of this approach has yet to be confirmed in phase III randomized controlled trials; moreover, distant failure remains a significant problem in patients with oligometastatic disease treated with SBRT. Given the propensity for distant failure in patients with oligometastatic disease treated with SBRT, there is growing interest in the utility of combining SBRT with systemic agents such as immunotherapy. Immunotherapy, and specifically immune checkpoint blockade (ICB), represents a rapidly evolving systemic therapy option with a growing number of indications among patients with metastatic disease; however, despite its promise, only a minority of patients respond to ICB and among those who do, the majority eventually progress. SBRT and ICB are both dependent upon, and have the ability to shift, the balance between antitumor immune surveillance and immunosuppressive states in the tumor and tumor microenvironment. As a result, it has been speculated that SBRT and ICB have the potential to act synergistically when used in combination. SBRT has been demonstrated to be safe in combination with ICB in studies with short-term follow-up and although additional research is needed, preliminary prospective data support the potential efficacy of this approach. In addition to confirming the safety and efficacy of SBRT in combination with immunotherapy, further studies are needed to determine how to maximize the therapeutic ratio of this treatment paradigm for the full potential of immunotherapy in the oligometastatic population to be realized.

Muscle Loss after Chemoradiotherapy as a Biomarker of Distant Failures in Locally Advanced Cervical Cancer.

This study aimed to evaluate whether computed tomography (CT)-based muscle measurement predicts distant failure in patients with locally advanced cervical cancer (LACC). Data from 278 patients with LACC who underwent chemoradiation therapy (CCRT) between 2004 and 2017 were analysed. Changes in the skeletal muscle index (SMI), skeletal muscle density, and total adipose tissue index during CCRT were calculated from CT images taken at the baseline and after CCRT. The predictive capability of CT-based muscle measurement for distant failure was evaluated using Cox proportional hazards regression, Harrell’s concordance index (C-index), and time-dependent receiver operating characteristic curves. SMI loss ≥ 5% was independently associated with worse distant recurrence-free survival (DRFS) (HR: 6.31, 95% CI: 3.18–12.53; p < 0.001). The addition of muscle change to clinical models, including International Federation of Gynaecology and Obstetrics (FIGO) stage, lymph nodes, pathology, and squamous cell carcinoma-antigen, achieved higher C-indices (0.824 vs. 0.756; p < 0.001). Models including muscle change had superior C-indices than those including weight change (0.824 vs. 0.758; p < 0.001). The area under the curve for predicting 3-year DRFS was the highest for the muscle-loss model (0.802, muscle-loss model; 0.635, clinical model; and 0.646, weight-loss model). Our study demonstrated that muscle loss after CCRT was independently associated with worse DRFS and that integrating muscle loss into models including classical prognostic factors improved the prediction of distant failure.

Neoadjuvant or Adjuvant Chemotherapy Plus Concurrent CRT Versus Concurrent CRT Alone in the Treatment of Nasopharyngeal Carcinoma: A Study Based on EBV DNA

The goal of this study was to explore the value of adding neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy (ACT) to concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC) with different risks of treatment failure. A total of 2,263 eligible patients with stage III-IVb NPC treated with CCRT ± NACT or ACT were included in this retrospective study. Distant metastasis-free survival (DMFS), overall survival, and progression-free survival were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. Patients in the low-risk group (stage N0-1 disease and Epstein-Barr virus [EBV] DNA <4,000 copies/mL) who received NACT followed by CCRT achieved significantly better 5-year DMFS than those treated with CCRT alone (96.2% vs 91.3%; P= .008). Multivariate analyses also demonstrated that additional NACT was the only independent prognostic factor for DMFS (hazard ratio, 0.42; 95% CI, 0.22-0.80; P=.009). In both the intermediate-risk group (stage N0-1 disease and EBV DNA ≥4,000 copies/mL and stage N2-3 disease and EBV DNA <4,000 copies/mL) and the high-risk group (stage N2-3 disease and EBV DNA ≥4,000 copies/mL), comparison of NACT or ACT + CCRT versus CCRT alone indicated no significantly better survival for all end points. The addition of NACT to CCRT could reduce distant failure in patients with low risk of treatment failure.

Disease Control and Survival Outcomes for Strut-Adjusted Volume Implant for Early-Stage Breast Cancer in ASTRO Consensus Guidelines Cautionary Groups for Accelerated Partial Breast Irradiation: A Single-Institution Experience

We report the outcomes for survival, local recurrence, and distant failure in patients treated with strut-adjusted volume implant (SAVI) for patients treated accelerated partial breast irradiation (APBI) treated at our institution groups by suitable and cautionary factors according to the ASTRO 2016 Consensus Guidelines for APBI. Patients treated from January 2013 to July 2015 with SAVI planned for 10 fractions at twice daily fraction regimen for a total dose of 34 Gy were included. Patients conforming to the ASTRO 2016 consensus guidelines for APBI were grouped into “Suitable” and respective “Cautionary” groups. Metrics for survival, recurrence, and progression were curated from chart review and imaging examinations. A total of 134 SAVI patients were treated within the analyzed period. Median follow up for all patients was 40.37 months. Those with adequate time to three-year follow-up totaled 44 patients in the ASTRO 2016 APBI suitability group, and 15, 14, 7, and 9 for age 40-49 years, estrogen receptor negative, invasive lobular carcinoma histology, and Grade 3 ductal carcinoma in situ cautionary groups, respectively. Results for overall survival, local control, and distant control are shown in Table 1.Abstract TU_5_3364; Table 1SuitableAge 40-49 yearsER negativeLobular HistologyGrade 3 DCIS3-year Overall Survival96%100%93%100%100%3-year Local Control96%73%86%100%100%3-year Distant FailureN/AN/A7%N/AN/A Open table in a new tab Our data suggest excellent local control and survival in ASTRO 2016 APBI cautionary groups with SAVI implants at 3 years. Certain cautionary features appear to portend worse outcomes, but further follow up and characterization will elucidate specifics in patient characteristics or treatment schema that may correlate with these outcomes. We will continue to document outcomes for patients enrolled within this time frame, as well as outcomes for patients enrolled after July 2015 to increase our sample size and identify pertinent outcomes and correlations.

A Novel Prognostic Nomogram for Predicting Risks of Distant Failure in Patients with Invasive Breast Cancer Following Postoperative Adjuvant Radiotherapy.

PurposeThis study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer.Materials and MethodsA total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model.ResultsThe 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029).ConclusionThe nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.

Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy

To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9months vs 22.0months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4months vs 24.2months, P=.0094) but not of local control. c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.

Concurrent Chemoradiation Therapy for Resected Gall Bladder Cancers and Cholangiocarcinomas

Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. This study compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients. We retrospectively analyzed all non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992 - 2016. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. All neoadjuvant treatment patients (chemotherapy alone, CRT or RT alone) were combined due to small numbers in each group. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence. Out of 128 patients, 90 had GBC and 38 had CCA. 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (58%) GBC and 25 (66%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (78 %) or radiation with or without chemotherapy 17 patients (22%). Chemotherapy was single agent in 47 patients (65%) and multi-agent in 25 (35%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (p=0.67). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (p=0.16). There was a trend towards increased distant failure in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI = (0.73- 10.36) p=0.14 and 0.92, 95% CI = (0.44-1.93) p=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI = (0.62- 16.31) p=0.16 whereas HR was 0.15, 95% CI = (0.10-1.76) p=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients who were given non-neoadjuvant treatment. In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors.

Induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

The value of adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. In our recent article entitled “Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial” published in the Lancet Oncology, we reported the results of a phase III, multicenter, randomized controlled trial comparing cisplatin, 5-fluorouracil, and docetaxel (TPF) IC plus CCRT versus CCRT alone in patients with T3-4N1/TxN2-3M0 NPC (ClinicalTrials.gov registration number NCT01245959). The IC-plus-CCRT group showed significantly higher 3-year failure-free survival, overall survival, and distant failure-free survival rates than the CCRT-alone group, with an acceptable toxicity profile. Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC. However, long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy, and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases

BackgroundStereotactic radiosurgery (SRS) is an alternative to post-operative whole brain radiation therapy (WBRT) following resection of brain metastases. At our institution, CyberKnife (CK) is considered for local treatment of large cavities ≥2 cm. In this study, we aimed to evaluate patterns of failure and characterize patients best suited to treatment with this approach.MethodsWe retrospectively reviewed 30 patients treated with CK to 33 resection cavities ≥2 cm between 2011 and 2014. Patterns of intracranial failure were analyzed in 26 patients with post-treatment imaging. Survival was estimated by the Kaplan-Meier method and prognostic factors examined with log-rank test and Cox proportional hazards model.ResultsThe most frequent histologies were lung (43 %) and breast (20 %). Median treatment volume was 25.1 cm3 (range 4.7–90.9 cm3) and median maximal postoperative cavity diameter was 3.8 cm (range 2.8–6.7). The most common treatment was 30 Gy in 5 fractions prescribed to the 75 % isodose line. Median follow up for the entire cohort was 9.5 months (range 1.0–34.3). Local failure developed in 7 treated cavities (24 %). Neither cavity volume nor CK treatment volume was associated with local failure. Distant brain failure occurred in 20 cases (62 %) at a median of 4.2 months. There were increased rates of distant failure in patients who initially presented with synchronous metastases (p = 0.02). Leptomeningeal carcinomatosis (LMC) developed in 9 cases, (34 %). Salvage WBRT was performed in 5 cases (17 %) at a median of 5.2 months from CK. Median overall survival was 10.1 months from treatment.ConclusionsThis study suggests that adjuvant CK is a reasonable strategy to achieve local control in large resection cavities. Patients with synchronous metastases at the time of CK may be at higher risk for distant brain failure. The majority of cases were spared or delayed WBRT with the use of local CK therapy.

Nuclear Hypoxia-Inducible Factor 1 Alpha is a Predictor of Distant Failure in Patients With Resected Pancreatic Adenocarcinoma

Nuclear Hypoxia-Inducible Factor 1 Alpha is a Predictor of Distant Failure in Patients With Resected Pancreatic Adenocarcinoma

MP13-03 IMPACT OF SYNCHRONOUS BLADDER CANCER ON RECURRENCE-FREE SURVIVAL AFTER SURGICAL TREATMENT FOR PRIMARY URETHRAL CANCER: RESULTS FROM THE INTERNATIONAL COLLABORATION ON PRIMARY URETHRAL CARCINOMA (ICPUC)

MP13-03 IMPACT OF SYNCHRONOUS BLADDER CANCER ON RECURRENCE-FREE SURVIVAL AFTER SURGICAL TREATMENT FOR PRIMARY URETHRAL CANCER: RESULTS FROM THE INTERNATIONAL COLLABORATION ON PRIMARY URETHRAL CARCINOMA (ICPUC)

Locoregional Lymphadenectomy in the Surgical Management of Anorectal Melanoma

The effect of lymph node metastasis on local tumor control and distant failure in patients with anorectal melanoma has not been fully studied. Understanding the significance of lymphatic dissemination might assist in stratifying patients for either organ preservation or radical surgery. A retrospective review of all patients with anorectal melanoma who underwent surgery at our institution between 1985 and 2010. Abdominoperineal resection (APR) was performed in 25 patients (39 %), and wide local excision (WLE) in 40 (61%). Extent of primary surgery and locoregional lymphadenectomy (mesorectal vs. inguinal vs. none) and pattern of treatment failure were analyzed. Recurrence-free survival (RFS) and disease-specific survival (DSS) were calculated. In patients undergoing APR, DSS was not associated with presence (29 %) or absence (71 %) of metastatic melanoma in mesorectal lymph nodes. There was a trend toward improved DSS in patients with clinically negative inguinal lymph nodes (n = 17) compared with patients with proven inguinal metastasis (n = 6; P = 0.12). Type of surgery (WLE vs. APR) was not associated with subsequent development of distant disease. Twelve patients (18 %) had synchronous local and distant recurrence. Synchronous recurrence was not associated with surgical strategy used to treat primary tumor (P = 0.28). Perineural invasion (PNI) was significantly correlated with RFS (P = 0.002). Outcome following resection of anorectal melanoma is independent of locoregional lymph node metastasis; lymphadenectomy should be reserved for gross symptomatic disease. PNI is a powerful prognostic marker warranting further exploration in clinical trials.

Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis

IntroductionOngoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes.MethodsOne hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC.ResultsMedian follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053).ConclusionsCompared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

PurposeTo determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent. MethodsFrom 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure. The cumulative LR failure (LRF) rate was calculated. Distant failure-free survival (FFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Volumetric images of LR failures were delineated and registered with the original radiation treatment plans if available. Dosimetric parameters for the delineated failure volumes were calculated from the original treatment information. ResultsThe median follow-up was 19months. The site of first failure was LR in 34, distant in 80 and simultaneous LR and distant in 31 patients. The cumulative LRF rate was 29% and 38% at 2 and 5years. OS was 44% at 2years. Seventy patients had electronically archived treatment plans of which there were 16 LR failures (7 local and 39 regional failure volumes). Of the local and regional failure volumes 29% and 31% were in-field, respectively. ConclusionsThe predominant pattern of LR failure was marginal or out-of-field. LR failures may be preventable with improved radiotherapy target definition.

Current treatment strategies of oesophageal carcinoma

Recent progress in the prognosis of patients with oesophageal cancer appears rather to reflect better patient selection and improved perioperative management than efficacy of the therapy. There are still a lot of controversies regarding treatment strategies due to lack of studies with adequate patient numbers and the inclusion of heterogeneous study populations. Surgery alone showed high rates of locoregional and distant failure for patients with locally advanced stages and consequently a 3 y-survival rate of only 15–20%. Postoperative radiotherapy and chemotherapy were usually not feasible due to the morbidity of the oesophagectomy. Preoperative chemotherapy showed a significant but only modest improvement in overall survival over surgery alone. Most studies investigating neoadjuvant chemoradiation were under-powered and showed no significant difference; however, in several meta-analyses a significant reduction of tumour related death rate could be shown at the expense of an increased postoperative mortality. Two European trials randomized mainly squamous cell cancer patients to chemoradiation with or without surgery. The designs of these two trials were slightly different. Both showed an increased mortality rate linked with surgery, a better locoregional control with surgery and no significant difference of overall survival according to their prospective hypothesis. The results of these trials have been controversially discussed. No general guideline of a treatment strategy is possible, because too many variables have to be considered such as histology, tumour localization, response to neoadjuvant therapy, co-morbidity, performance status and age of the patient. Personal conclusions and recommendations of the authors were discussed.

Comparison of Two Adjuvant Chemoradiotherapy Protocols after Resection of Primary Pancreatic Carcinoma: A 10 Year Experience

The purpose of this study is to describe 10-year follow-up of two prospective adjuvant chemoradiation (CRT) protocols with regards to overall survival (OS), local recurrence, and distant failure in patients with primary pancreatic adenocarcinoma.

Prediction for distant failure in patients with stage M0 nasopharyngeal carcinoma: The role of standardized uptake value

Distant failure is an important cause of death in stage M0 primary nasopharyngeal carcinoma (NPC). However, a reliable prognosticator for occurrence of distant failure was lacking. Thus, we conducted this study to investigate prospectively the role of standardized uptake value on 18F-FDG for predicting distant failure in stage M0 NPC. Patients with stage M0 primary NPC diagnosed by both conventional work-up (CWU) and 18F-FDG PET were enrolled. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards models were used to identify independent prognosticators. Between January 2002 and July 2003, 65 NPC patients were investigated. Up to the date of analysis, 12 patients died and 13 patients experienced recurrences, among whom 9 had distant failures. The 5-year overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS) were 81.2%, 79.2%, 84.4%, respectively. In multivariate analysis, the following risk factors for poor prognosis were identified: T3-4 (p=0.033) for RFS; and maximal standardized uptake value (SUVmax) of the primary tumor > 12.0 (p=0.012), stage IVa-b (p=0.037), and N2-3 disease (p=0.04) for DRFS. The 5-year DRFS in stage IVa-b patients with SUVmax > 12.0 was significantly lower than that in stage I-III patients with SUVmax < or = 12 (p=0.0001). None of the patients in the latter group developed distant failure. In conclusion, a SUVmax > 12.0 of the primary tumor represents a "metabolic phenotype" for occurrence of distant failure in stage M0 NPC patients. And the combined information of SUVmax and tumor staging can guide the use of neoadjuvant/adjuvant therapy and surveillance protocols to improve distant control.

Timing of Local Versus Distant Failure in Patients With Early-Stage Lung Cancer: Is the Risk of Local Failure Underreported?

Timing of Local Versus Distant Failure in Patients With Early-Stage Lung Cancer: Is the Risk of Local Failure Underreported?