Patterns Of Failure In Patients Research Articles

Proton Beam Therapy for Unresectable Cholangiocarcinoma

To evaluate the treatment outcome and patterns of failure in patients with unresectable cholangiocarcinoma undergoing proton beam therapy (PBT). We retrospectively analyzed 22 patients with pathologically confirmed cholangiocarcinoma who were treated with definitive PBT from November 2015 to August 2017. Four-dimensional computer tomography (4D-CT) with and without intravenous contrast-enhancement was acquired with 2.5 mm slide thickness. A clinical target volume expansion of 5-10 mm was used. The internal target volume was generated based on the 4D-CT images, and respiratory gaiting was adopted in patients with tumor motion >10 mm. Treatment-related toxicities were recorded according to Common Terminology Criteria for Adverse Event version 4.0 (CTCAE v4.0). The study included 11 male and 11 female participants, with a median age of 68 years (range, 46-88 years). Intrahepatic, perihilar and distal extrahepatic, and gallbladder tumors were recorded in 12 (54%), 7 (32%), 1 (5%) and 2 (9%), respectively. The median tumor dimension was 7.0 cm (range, 3.8-18.2 cm). Stage IV, III and II was documented in 15 (68%), 5 (23%) and 2 (9%) patients, respectively. Tumor vascular invasion was observed in 5 (23%) patients, and 19 (86%) patients demonstrated biliary tract obstruction. The median PBT dose was 72.6 cobalt gray equivalent (CGE) (range, 39.6-72.6 CGE). Gemcitabine-based concomitant chemotherapy was administered in 15 (68%) patients. After a median follow-up of 14.3 months, the 1-year overall survival rate was 75%. Fifteen (68%) patients developed disease progression. Among them, one (5%) patients experienced in-field local failure, whereas 4 (18%) patients developed intrahepatic out-field recurrence. Distant metastasis (N = 10, 45%) was the predominant form of treatment failure. The 1-year local control and progression-free survival rates were 100% and 42%, respectively. Among the 19 patients who presented obstructive jaundice, normalization of total bilirubin level was recorded in 14 (74%) patients after PBT with or without biliary drainage. Grade 3 dermatitis and grade 4 duodenal ulcer occurred in 2 (9%) and 2 (9%) patients, respectively. PBT could lead to an excellent local control probability, sustainable relief of biliary tract obstruction and a favorable survival outcome in patients with unresectable cholangiocarcinoma. However, distant recurrence remains the primary reason of failure after PBT.

Patterns of Failure for Patients Treated for Synchronous Primaries with SBRT

Patterns of Failure for Patients Treated for Synchronous Primaries with SBRT

Patterns of failure in rectal cancer with positive circumferential resection margin after surgery following preoperative chemoradiation: a propensity score matching analysis.

To compare the patterns of failure between rectal cancer patients with negative and positive circumferential resection margin (CRM) after surgery following preoperative chemoradiation. Of 944 stage II-III rectal cancer patients treated with radical surgery following preoperative chemoradiation, 74 patients (7.8%) showed positive CRM. Each 72 patients from negative and positive CRM groups were identified by propensity score matching and compared in terms of survival outcomes and patterns of failure. Local failure was defined as recurrence at the anastomosis site or adjacent to the mesorectal fascia. The median follow-up was 46 months (range, 4-155). No difference was observed in 5-year local recurrence-free survival (93.4% vs 89.6%, p = 0.442) in the negative and positive CRM groups. There was statistically significant difference in relapse-free survival (57.1% vs 39.1%, p = 0.042). Negative CRM group showed favorable outcomes than positive CRM in distant metastasis-free survival (59.4% vs 43.3%, p = 0.069) and overall survival (67.5% vs 55.8%, p = 0.186), but the difference was not statistically significant. As the initial failure pattern, there were 30 and 43 recurrences in the negative and positive CRM groups (local 6.6 and 7.3%, regional 12.8 and 14.4%, and distant 38.5 and 54.9%). Isolated local recurrence was identified in two with negative CRM and in none with positive CRM (p = 0.497). Distant metastasis was the major pattern of failure regardless of CRM involvement in rectal cancer patients treated with surgery following preoperative chemoradiation. It would be taken account of our finding on adjuvant treatment for the patient with positive CRM. Investigation of the patterns of failure in patients with CRM involvement after preoperative chemoradiation followed by surgery can be conducive to selecting the appropriate approach to additional treatment for them.

Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma

BackgroundThe 8th edition American Joint Committee on Cancer staging system for resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number as a critical determinant of survival. We sought to characterize outcomes and patterns of failure in patients with high pathologically involved node number oropharynx cancer. MethodsWe retrospectively identified 116 HPV+ OPC patients sequentially treated with neck dissection and either resection or intraoperative brachytherapy of the primary tumor between 2010 and 2016. External beam radiation was given based on the pathologic findings. Cox proportional hazards regression was used for multivariate analysis. ResultsWith a median follow-up of 27 months, the 3-year overall survival and progression free survival (PFS) were 89% and 81%, respectively. On multivariate analysis, ≥5 involved lymph nodes was significantly associated with worse PFS (hazard ratio 4.3, 95% confidence interval (CI) 1.5–12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR) in patients with ≤4 vs ≥5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year distant metastases (DM) were 12% and 53% between ≤4 and ≥5 (log-rank P < 0.001). ConclusionOur findings confirm that patients with 5 or more involved lymph nodes appear to have substantially worsened rates of disease recurrence. While these patients appear to be at high risk of both LRR and DM, the predominant mechanism of failure is distant, and the rate of DM in this group was over 50%. Dedicated clinical trials in this patient population are warranted with a focus on mitigating the high DM rate.

Patterns of failure following the excision of in-transit lesions in melanoma and the influence of excisional margins.

To describe the patterns of failure in patients with in-transit (IT) melanoma undergoing surgical excision. A retrospective review of patients who underwent their first IT lesion(s) resection between May 2005 and September 2014. Cumulative incidence of local failure (new lesion within 2 cm of IT resection) was estimated. Associations between clinicopathologic characteristics, local failure, and any recurrence were analyzed. One hundred and thirty patients presented to our institution with IT disease over the study period and met the inclusion criteria. The 2-year cumulative incidence of local failure was 19.5%. Twenty-four patients developed disease within 2 cm of the resected IT disease; however, only eight were isolated local events. Cumulative incidence of local failure and of any disease differed with respect to less than 1 year disease-free interval (DFI) from primary melanoma to first IT event, and having greater than 1 IT lesion at presentation. Incidence of local failure was not found to differ with respect to gross margin greater than 5 mm, after adjusting for DFI and greater than 1 IT lesions. Patients with greater than 1 IT lesion and a DFI less than 1 year are at a higher risk of failure after surgical excision of a first IT event. Very few failures were isolated local disease within 2 cm of the IT resection scar, regardless of IT excision margin.

Metabolic positron emission tomography parameters predict failure patterns in early non-small-cell lung cancer treated with stereotactic body radiation therapy: a single institution experience.

The prognostic value of metabolic parameters using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has not been established for early non-small cell lung cancer (NSCLC). Accordingly, the authors investigated the prognostic value of metabolic parameters in terms of failure patterns in patients with early NSCLC who underwent stereotactic body radiation therapy (SBRT). Data from 35 patients with Stage I NSCLC who underwent SBRT using CyberKnife and received pretreatment FDG PET/CT between 2008 and 2016 were retrospectively reviewed. Maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were measured. The significance of these parameters with regard to failure patterns was assessed. The median follow-up was 23 months for all patients and 34 months for living patients. Ten patients experienced recurrence: three local failures, five regional failures (RF), and eight distant failures (DF). Three-year local, regional and distant control rates were 96.7%, 86.4% and 71.1%, respectively. High SUVmax (<9 vs. ≥9) was an independent predictive factor associated with increased RF (P = 0.027) and DF (P = 0.008). Furthermore, SUVmax was indicative of both progression-free (P = 0.015) and overall (P = 0.034) survival. High SUVmax was a significant metabolic parameter associated with increased RF and DF in patients with early NSCLC who received SBRT, having a high propensity for dissemination. These results suggest that adjuvant treatment in conjunction with SBRT may be considered in patients with early NSCLC and high SUVmax.

Survival outcomes and patterns of failure after D2 dissection and adjuvant chemoradiotherapy for locally advanced gastric cancer: a retrospective study.

The goal of the study was to analyze the incidence and patterns of failure in patients with gastric cancer who received D2 dissection and adjuvant chemoradiotherapy (CRT). From January 2004 to October 2015, 324 patients with gastric cancer who underwent radical D2 resection followed by postoperative CRT were enrolled. Clinicopathological characteristics and patterns of failure were retrospectively reviewed to identify factors associated with survival and recurrence. After a median follow-up of 30 months, the 3-year overall survival and 3-year disease-free survival rates of these patients were 60.3 and 51.1%, respectively. 117 patients had recurrence or metastasis, with peritoneal recurrence as the most frequent (20.7%), followed by distant metastasis (14.2%). The most commonly involved distant organs were the liver (5.9%) and bone (4.9%). Locoregional failure occurred in 39 patients (12.0%), with isolated regional failure occurring in only 23 (7.1%). Further multivariate Cox regression analysis revealed N stage to be an independent risk factor for distant failure-free survival (p=0.012). Independent risk factors for peritoneal metastasis were tumor differentiation (p=0.022), T stage (p=0.035) and vascular invasion (p=0.016). Postoperative CRT has a potential effect on optimizing locoregional control, resulting in only 12.0% of locoregional failure. In patients after D2 resection and adjuvant CRT, peritoneal metastasis was the leading pattern of failure, followed by distant metastasis. Advances in knowledge: Peritoneal recurrence was the most common pattern of failure after D2 dissection and adjuvant CRT, followed by distant metastasis, whereas locoregional relapse was relatively rare. Selection of patients based on the predicted risk of each recurrence pattern may be a reasonable approach to the optimization of treatment strategies.

Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy

Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P=.04). DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.

Early Clinical Outcomes, Patterns of Failure, and Acute Haematologic Toxicity of Image-Guided Volumetric Modulated Arc Therapy (IG-VMAT) in the Definitive Treatment of Locally Advanced Carcinoma Cervix.

Purpose:To evaluate clinical outcomes and failure patterns in patients with locally advanced cervical cancer (LACC) treated definitively using image-guided volumetric-modulated arc therapy (IG-VMAT).Methods and materials:This retrospective review included 18 consecutively treated patients with LACC. Treatment consisted of IG-VMAT and concurrent chemotherapy followed by intracavitary radiotherapy. The primary end points were overall survival (OS) and disease-free survival (DFS). Acute haematologic toxicity was evaluated using Radiation Therapy Oncology Group (RTOG) criteria.Results:A total of 16 patients were either stage IIB or IIIB and the median follow-up was 30.5 months (interquartile range: 13-36.25 months). The 2-year DFS was 63.3% (95% confidence interval [CI]: 52.8%-72.4%) and 2-year OS was 72.2% (95% CI: 62.1%-80.5%). There were 7 treatment failures, predominantly in-field. Acute haematologic toxicity was low.Conclusions:IG-VMAT is associated with favourable outcomes for patients with LACC.

Analysis of the causes of failure after radical surgery in patients with PT3N0M0 thoracic esophageal squamous cell carcinoma and consideration of postoperative radiotherapy

BackgroundFive-year overall survival rate of TESCC after surgery is low (approximately 30% to 60%), so it is meaningful to discuss the significance of PORT.MethodsWe retrospectively collected the data of 227 patients with PT3N0M0 esophageal cancer (EC). The failure pattern after surgery was analyzed. Difference of adjuvant PORT in patients with PT3N0M0 TESCC and the appropriate population were explored based on the relevant studies.ResultsThere were 58 cases with intrathoracic locoregional recurrence (LRR) after radical surgery and 27 cases with distant metastasis, including 10 cases of recurrence. The recurrence rate of mediastinal lymph nodes in the thoracic cavity was 50.0%. Univariate analysis revealed that compared with patients with middle and lower thoracic EC, the 3/5-year survival rate of patients with upper thoracic EC was significantly lower, accompanied with remarkably higher thoracic LRR. Compared with those with moderately- and well-differentiated TESCC, the 3/5-year survival rate of patients with poorly differentiated TESCC was significantly lower, whereas the distant metastasis rate was notably higher. Multivariate analysis revealed that different lesion locations and different pathologic differentiation were the independent prognostic factors. The lesion location and degree of differentiation were the independent influencing factors for thoracic LRR and distant metastasis, respectively.ConclusionThe intrathoracic LRR is the major failure pattern for patients with PT3N0M0 TESCC after conventional two-field lymphadenectomy. In addition, recurrence rate of PT3N0M0 TESCC was significantly higher in upper thoracic EC than in middle and lower thoracic EC. PORT is recommended to patients with PT3N0M0 upper TESCC.

Re-Irradiation for Recurrent Pediatric Ependymoma

Long-term outcomes and optimal dose and volume for re-irradiation of relapsed pediatric ependymoma (EP) are unknown. Patients with recurrent EP treated with a second course of fractionated radiation (RT2) were retrospectively reviewed. Eligible patients had intracranial EP at diagnosis treated with focal irradiation (RT1) without craniospinal irradiation (CSI) and were age ≤21. Progression-free (PFS) and overall survival (OS) were counted from the first day of RT2. Patients were assessed for 1q gain and a C11orf95-RELA fusion based on tumor location. Ninety-eight patients were included with a median follow-up of 32.0 months (IQR, 13.8-78.8). Median doses of RT1, focal RT2, and CSI were 59.4, 54, and 39.6 Gy, respectively. Median time between RT1 and RT2 was 27.1 months (IQR = 18.0-43.1). Median PFS was 27.3 months (95% CI = 16.4-45.7) and median OS was 75.1 months (95% CI = 44.3-159). CSI was not associated with OS in patients with RT1 local failure (LF; HR = 1.7, P = .25). Thirty-one patients with LF after RT1 had progression after RT2; none who had received RT2 CSI (n = 7) developed distant-only failure (DF), whereas 42% who received focal RT2 (n = 24) developed distant-only failure. Among infratentorial tumors with progression after focal RT2, distant-only failure was seen in 31% (1q gain absent, n = 13) and 80% (1q gain present, n = 5). The 1q gain, observed in 41% of infratentorial tumors, was associated with reduced OS among patients with RT1 distant failure (HR = 3.5, P = 0.029), but not RT1 LF (HR = 0.7, P = 0.55). C11orf95-RELA fusion, which was seen in 67% of supratentorial tumors, was not associated with OS (HR = 1.5, P = 0.62). Factors associated with OS in a multivariable analysis are listed in the Table 1. Initial site of disease, extent of resection before RT2, chemotherapy prior to RT2, time-to-RT1 failure, and CSI were not independently associated with OS. The actuarial rate of grade ≥3 necrosis was 7.0% (95% CI = 3.3-15.0), with median time of onset of 8.6 months after RT2. Re-irradiation for relapsed pediatric ependymoma results in long-term survival for many patients. Patients with 1q gain are at risk of distant failure. RT2 CSI changes the pattern of failure in patients with local-only failure after RT1, with no distant failures observed. Novel biomarkers to select patients who benefit most from CSI are needed.Tabled 1Abstract 126; Table 1Factors associated with OSnMedian OS, months (95% CI)Adjusted HR (95% CI)PPattern of failure/RT2 treatmentLF/focal44160.0 (44.1-NR)RefLF/CSI952.5 (13.7-NR)1.0 (0.38-2.7).97DF/CSI31136.6 (60.1-159.4)0.36 (0.17-0.74).018LF + DF/CSI1416.1 (12.5-364.7)2.2 (0.91-5.3).081SexMale6244.1 (22.7-74.9)RefFemale36141.6 (75.1-364.7)0.36 (0.17-0.74).006WHO grade at recurrenceII72364.7 (125.8-364.7)RefIII2352.5 (26.2-75.1)4.7 (1.8-12.3).002Time from RT1 to RT2 (per year)980.75 (0.58-0.96).023 Open table in a new tab

Outcomes of invasive mediastinal nodal staging versus positron emission tomography staging alone for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy

BackgroundThe benefit of invasive mediastinal nodal staging (IMNS) in addition to positron emission tomography-computed tomography (PET/CT) is undefined for early stage non-small cell lung cancer (NSCLC). This multi-institutional investigation aimed to evaluate outcomes and patterns of failure in patients staged with PET/CT with or without additional IMNS. MethodsTwo academic centers assessed all consecutive patients staged with PET/CT for early-stage, primary lung NSCLC (cT1-2aN0M0) treated with SBRT. Local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes. ResultsOverall, 180 patients (199 lesions) were staged with PET/CT alone and 56 patients (58 lesions) underwent additional IMNS. Among patients receiving IMNS, 52 (93%) underwent EBUS and 4 (7%) underwent mediastinoscopy. At a median follow-up of 33.5 months (range, 1.9–80.9 months), there was no significant difference in LRFS (37 vs. 47 months, p=0.309), NRFS (34 vs. 42 months p=0.370), DMFS (36 vs. 47 months, p=0.234) or OS (37 vs. 47 months, p=0.236) between patients undergoing PET/CT-only versus PET/CT+IMNS staging, respectively. Receipt of IMNS did not correlate with any outcome on either univariate or multivariate analysis (p>0.05). Patterns of failure in both groups were similar, including crude isolated nodal failure rates (8% PET/CT-only versus 14% PET+IMNS group, p=0.202). ConclusionsPatients undergoing IMNS had similar survival and patterns of recurrence as those receiving PET/CT alone. Further study, ideally prospectively, is needed to determine which subgroups might benefit from IMNS.

Cystic nodal metastasis in patients with oropharyngeal squamous cell carcinoma receiving chemoradiotherapy: Relationship with human papillomavirus status and failure patterns.

ObjectivesWe investigated the relationships of cystic nodal metastasis, human papillomavirus (HPV) status, and treatment failure patterns in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with chemoradiotherapy.MethodsWe retrospectively reviewed pretreatment MRI and clinical courses of patients with OPSCC whose tumors were tested for HPV-induced p16 expression via immunohistochemistry and who completed chemoradiotherapy. Cervical cystic nodal metastasis and necrotic nodal metastasis were classified on MRI.ResultsOf 98 patients eligible for analysis, 33 were p16-positive. Cystic nodal metastasis was significantly more prevalent in p16-positive than in p16-negative patients (39.4% versus 18.5%, respectively; p = 0.025). Necrotic nodal metastasis was significantly more prevalent in p16-negative than in p16-positive patients (73.8% versus 51.5%, respectively; p = 0.027). On multivariate analysis, necrotic nodal metastasis (odds ratio [OR] = 7.310, p = 0.011) was an independent predictor of regional failure, while advanced nodal stage (OR = 4.119, p = 0.022) and cystic nodal metastases (OR = 0.087, p = 0.026) were independent positive and negative predictors of distant failure, respectively.ConclusionsCervical cystic and necrotic nodal metastases are associated with HPV-induced p16-positive and p16-negative OPSCC, respectively. Patients with necrotic nodal metastasis at presentation have an increased risk of regional failure. Distant failure is directly and inversely correlated with advanced nodal stage and cystic nodal metastasis, respectively.

EP-1096: Using DIR to study patterns of loco-regional failure in patients with head and neck cancer

EP-1096: Using DIR to study patterns of loco-regional failure in patients with head and neck cancer

Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice

Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns. The 10-year overall survival rates of LA, LB-HER2(-), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P<0.001). Distant metastatic events differed significantly according to molecular subtype (P<0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(-), and LB-HER2(+) subtypes (P=0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P=0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5years. From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.

Patterns of failure for patients with glioblastoma following O-(2-[18F]fluoroethyl)-L-tyrosine PET- and MRI-guided radiotherapy

Background and purposeTo evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. Materials and methodsThe first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria. ResultsFifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PETvol and the composite MRPETvol, respectively. MGMT-methylation (p=0.03), larger PETvol (p<0.001), and less extensive surgery (p<0.001), were associated with larger PETvol overlap. ConclusionThe combined MRPETvol had a stronger association with the recurrence volume than either of the modalities alone. Larger overlap of PETvol and RV was observed for patients with MGMT-methylation, less extensive surgery, and large PETvol on the RT-planning scans.

Histologic Subtype of Early-Stage Lung Adenocarcinoma Predicts Failure Patterns in Patients Treated With Stereotactic Body Radiation Therapy

Histologic Subtype of Early-Stage Lung Adenocarcinoma Predicts Failure Patterns in Patients Treated With Stereotactic Body Radiation Therapy

Clinical review of treatment outcomes and patterns of failure with adjuvant radiotherapy in node-positive malignant melanoma.

Adjuvant radiotherapy is proven to prevent lymph node field relapse after therapeutic lymphadenectomy for melanoma, but does not improve overall survival based on current data. There remains a high rate of distant relapse. This study reports patterns of failure in patients treated with adjuvant radiotherapy, looking at factors associated with distant metastasis and comparing this to recent literature. This retrospective study included patients treated with adjuvant nodal irradiation after lymphadenectomy between June 2012 and March 2015. Twenty-one patients were treated during this period. Median follow-up was 13.5months. There were no lymph node field recurrences. Distant metastasis (DM) rate was 48%. DM rate was significantly higher (P=0.027) in patients with extracapsular extension (ECE) (71%) than those without ECE (0%). DM rate was higher in those with a maximum tumour size of >3cm (71%) than those with tumour size <3cm (30%) (P=0.160). Number of nodes, BRAF status or nodal site did not correlate with rate of DM. The median time to DM was 16weeks after completion of radiotherapy. Radiotherapy is well tolerated and effective in regional control. However, patients are at risk of early distant relapse, particularly those with ECE or large tumour size. There are currently no useful prognostic markers to differentiate the risk of regional versus distant recurrence, and the optimal treatment paradigm remains undefined. Research on adjuvant systemic therapies and abscopal effects of radiotherapy have shown improved management of distant metastasis; creating an even greater need for effective regional control strategies.

T4/N2 classification nasopharyngeal carcinoma benefit from concurrent chemotherapy in the era of intensity-modulated radiotherapy.

Although the benefits of concurrent chemotherapy (CC) in the treatment of locally advanced nasopharyngeal carcinoma (NPC) had been proven in the era of two-dimensional radiotherapy, long-term efficacy and safety of using CC combined with intensity-modulated radiotherapy (IMRT) remain unclear. A retrospective analysis of 1,182 patients who underwent IMRT for clinical II-Iva NPC was performed. Propensity score matching algorithm was used to identify two matched cohorts with or without CC (264 patients per cohort). Median follow-up time was 45.6 and 43.6 months for the two cohorts. The estimated 5-year overall survival rate was 81.8% (95% CI 76.6-87.4) in patients treated with CC and 73.7% (95% CI 67.8-80.0) in those treated without CC, respectively (hazard ratio 0.64, 95% CI 0.44–0.93; p = 0.018). The benefit of CC was mainly observed in those patients with good performance status, male, age > 48 years, T4 and N2 classification. Grade 3/4 acute toxicities were more common in those patients administrated with CC. The grade and incidence of late salivary glands damage were also increased by CC (p = 0.003). These findings indicated that the addition of CC significantly improved treatment outcomes of NPC patients treated with IMRT, but accompanied increased toxicities. Tailored CC and optimizing schedule of IMRT and systemic therapy were needed, provided that distant metastasis was the predominant pattern of failure in patients treated with IMRT.

Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy

PurposeTo compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy.Methods and materialsTwo hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review.ResultsOne hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status.ConclusionsOur analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region.