Local-regional Recurrence Research Articles

Inadequate target volume delineation and local–regional recurrence after intensity-modulated radiotherapy for human papillomavirus-positive oropharynx cancer

PurposeTo perform a spatial analysis of local–regional recurrences, in relation to quantitative dose distribution, among patients treated by intensity-modulated radiotherapy (IMRT) for human papillomavirus (HPV)-positive oropharyngeal cancer. Methods and materialsThe records of 107 consecutive patients who presented for consideration of re-irradiation for local–regional recurrent disease occurring in a previously irradiated field were reviewed. The original IMRT plans were retrieved for those with HPV-positive disease originating from the oropharynx, and deformable image registration was used to fuse the magnetic resonance imaging (MRI) and positron emission tomography (PET) scans obtained at recurrence to the pre-treatment planning computed tomography (CT) dataset. The recurrent tumor volume (Vrecur) was subsequently identified on axial imaging, and the dose of radiation received by Vrecur was then calculated and analyzed using dose–volume histograms. ResultsA total of 83 recurrent lesions occurring in 50 oropharyngeal cancer patients were HPV-positive and met inclusion criteria. Using PET-defined Vrecur, thirty-three lesions were classified as in-field recurrences (40%), 35 were marginal misses (41%), and 15 were true misses (18%). Using the MRI-defined Vrecur, thirty-seven lesions were classified as in-field recurrences (45%), 32 were marginal misses (39%), and 14 were true misses (17%). ConclusionA significant proportion of local–regional recurrences from HPV-positive oropharyngeal cancer represented geographical misses which possibly could have been prevented with more meticulous attention to IMRT planning. This finding has important implications with respect to ongoing attempts to de-escalate radiation dose for this disease. Our data highlight the importance of robust quality assurance with careful review of target volumes prior to the initiation of IMRT.

Benefits of postoperative thoracic radiotherapy for small cell lung cancer subdivided by lymph node stage: a systematic review and meta-analysis.

Whether postoperative thoracic radiotherapy (PORT) is beneficial for small cell lung cancer (SCLC) of different lymph node stages remains uncertain; therefore, the purpose of this meta-analysis was to explore the clinical significance of PORT for SCLC patients subdivided by lymph node status. The PubMed, OVID, Web of SCI, EMBASE, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were systematically searched to identify eligible studies where SCLC patients received PORT based on lymph node stage. The main outcome measures were 1-, 3- and 5-year overall survival (OS) rates, as well as 1-, 2- and 3-year local regional recurrence (LRR) rates. All data were analyzed using STATA 12.0 and expressed as risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). Five cohort studies, including 3,497 SCLC patients (578 receiving PORT and 2,919 not) were included in this study. PORT significantly decreased the 1-, 2- and 3-year LRR rates (RR =0.14, 0.28 and 0.27, respectively; Pall<0.05), but did not improve the 1-, 3- or 5-year OS rates when all patients were analyzed together. However, subgroup analysis showed that in the pN0 group PORT did not improve the 1-, 3- or 5-year OS rates or decrease the 1-, 2- or 3-year LRR rates; in the pN1 group PORT reduced the 1-, 2- and 3-year LRR rates (RR =0.11, 0.16 and 0.17, respectively; Pall<0.05) and improved the 1-year OS rate (RR =0.40; P<0.001), but not the 3- or 5-year OS rates; in the pN2 group PORT significantly reduced the 1-, 2- and 3-year LRR rates (RR =0.14, 0.15 and 0.15 respectively; Pall<0.05) and improved the 1-, 3- and 5-year OS rates (RR =0.46, 0.72 and 0.85, respectively; Pall<0.05). This is the first meta-analysis of the benefits of PORT for SCLC patients. Although derived from retrospective cohort studies, the data showed that PORT significantly reduced the risk of recurrence and improved survival for patients with pN2-SCLC; however, patients with pN0-SCLC did not benefit from PORT, whereas for patients with pN1-SCLC, PORT reduced the LRR rates and improved the 1-year survival rate. The long-term survival benefits of PORT remain unclear and will require further prospective studies.

Parotid adenoid cystic carcinoma: Retrospective single institute analysis

PurposeAdenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. Materials and methodsWe retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). ResultsTwenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. ConclusionsRecurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis.

Multicystic peritoneal mesothelioma: A short review

Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, predominantly affecting female patients during their reproductive years. The lesion is usually distributed diffusely in the abdomen and pelvis, but the peritoneum of the pelvic organs is the most common site. MCPM is composed of fluid-filled translucent cysts, connected by varying amounts of fibrous tissue, and lined by a layer of mesothelial cells. Because of the rarity of this disease, the pathogenesis and natural history of MCPM remain poorly understood and continuously debated. Some authors consider it to be a reactive process for its association with prior surgery or abdominal inflammation. But its high rate of local-regional recurrence, as well as its malignant potential, suggests a neoplastic etiology. Preoperative diagnosis is often very difficult. Imaging methods, such as ultrasound, computed tomography, and magnetic resonance imaging, are of little value for an accurate diagnosis of MCPM. The definitive diagnosis relies on histologic examination of target lesions combined with immunohistochemical stains. There is no consensus on the clinical management of MCPM, although surgical removal remains the first-line treatment of choice. But no standards have been reached concerning which surgical options—traditional debulking surgery or more aggressive one—should be chosen. Alternative therapeutic approaches include hand-off treatment, hormonal supplementation, laser vaporization, and sclerotherapy, and they all come with uncertain results. Moreover, the lesions show no response to adjuvant chemotherapy and radiotherapy. This article aimed to focus on those controversial problems in pathogenesis, natural history, diagnosis, and treatment strategies to help medical workers to better understand this rare disease.

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer

BackgroundPrevious data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy.MethodsMedical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ2 test.ResultsA total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815).ConclusionThis retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.

Abstract P5-16-08: Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy

Abstract Purpose: We seek to investigate the prognostic factors that could possibly affect the local-regional recurrence (LRR) of breast cancer patients who do not achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NCT), and to build a prognostic nomogram to predict patients' outcome. Methods: The retrospective analysis included 510 patients who had received NCT followed by surgery and radiotherapy. The NCT regimens included anthracycline-containing, vinorelbinecontaining, and taxane-containing regimens for a median of 3 cycles. The clinical responses to neoadjuvant chemotherapy were evaluated based on MRI and ultrasound examinations and in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Miller-Payne (MP) grading system was employed to evaluate the decrease in cancer cellularity. Multivariate analyses were used to identify independent predictors of LRR. Results: The median follow-up for the entire study population was 61 months (range 5-128 months). There were 40 isolated local recurrences, 17 regional-only recurrences and 5 patients with local and regional recurrences. Sixteen patients (25.8%) occurred synchronously with distant metastasis, and no LRR was detected after distant failure. Fifteen patients had recurrences in the supraclavicular field. The 5-year cumulative LRR-free survival rate was 88.0% (95% CI: 85.2%-90.1%). The 5-year overall survival and disease-free survival rates were 79.0% (75.5%-82.6%) and 63.1% (58.9%-67.3%), respectively. Multivariate analysis revealed that positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% were independent factors for LRR-free recurrence. The prognostic model was established based on the sum of both independent prognostic factors, with positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% individually contributing 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 point), median-risk group (1 point) and high-risk group (2 points). The 5-year LRR-free survival rates in the low, intermediate, and high-risk groups were 95.5%, 89.1%, and 67.1%, respectively (p &amp;lt; 0.001). We also show the annual LRR rate among these 3 groups using our single-institution data, as well as to review relevant literature-based data to compare with our observations. Four publications that reported ARR (annual recurrence rate) after surgery for primary breast cancer were identified as eligible. In the relevant literature, the annual risk of local-regional recurrence peaked between two and three years after the initial diagnosis. In contrast, the ARR curve of the high risk subgroup for neoadjuvant patients exhibited one peak near 1 year (17% per annum). The median and low-risk subgroups did not have an obvious recurrence peak. Conclusion: This prognostic model has considerable clinical value in predicting local-regional recurrence, which could help clinicians to design appropriate local-regional treatment specifically and to perform surveillance individually. Citation Format: Chen S, Huang L, Shao Z-M. Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-08.

Abstract P1-10-13: Can the risk of radiation-induced cardiac disease in breast cancer be mitigated with cardiac-sparing techniques?

Abstract Introduction: Data suggest that long-term survivors of breast cancer treated with radiation therapy (RT) have an increased risk of cardiac events despite an overall survival benefit, particularly women with left-sided breast cancers. We hypothesized that with cardiac-sparing radiation techniques there would be no difference in long-term cardiac risks between women with right- and left-sided breast cancers. Materials and Methods: The outcomes of 775 consecutive women treated between 1984 and 1999 with breast-conserving therapy (BCT) (n=424) and post-mastectomy radiation therapy (PMRT) (n=351) for stage 0-3 breast cancer were assessed retrospectively through a review of medical records and contact with living patients. The choice of BCT vs PMRT was based on tumor board disposition and patient preference; mastectomy was recommended for multicentric or T3 breast cancers. Ninety-six percent of all node-positive patients received treatment to all nodal regions, including the internal mammary (IM), axillary (AX), and supraclavicular (SC) nodes. BCT patients had computed tomography-planned tangential breast radiation with photons with IM nodes treated within the tangent fields or with a separate en face electron field to minimize cardiac exposure. PMRT patients were treated with en face electron fields for the chest wall and IM for sparing of the lung and heart. The AX and SC nodes were treated with a matched anterior photon field with a posterior-anterior boost field (PAB) when necessary to achieve adequate dose in the AX with both BCT and PMRT. Overall, 411 patients were node-negative and 353 were node-positive. All patients have a minimum potential follow-up of 16.4 years; median actual follow-up for the BCT group was 15 years (range, 0.1-31.2) and for the PMRT group it was 9.5 years (range, 0.1-30.5). Results: Overall survival (OS), cause-specific survival (CSS), and freedom from local-regional recurrence (FFLR) rates for the cohort at 15 years were 58.2%, 72.0%, and 90.8%, respectively. Rates of freedom from cardiac events (FFCE), pulmonary events, and second malignancy were 87.6%, 93.6%, and 86.3%, respectively. On multivariate analysis, OS was correlated with stage (p=.045), number of positive nodes (p=.002), age (p&amp;lt;.0001), diabetes (p =.0021), and modality (p=.0017). Not surprisingly, 15-year survival for patients treated with BCT was better than for patients treated with PMRT (70.9% vs 59.7%; p&amp;lt;.0001). CSS was associated with stage (p=.0207), number of positive nodes (p=.0409), and modality (p=.0003). FFLR was associated with number of positive nodes (p=.0484). FFCE was associated with pretreatment cardiac disease (p&amp;lt;.0001), stage (p=.0461), and age (p=.0056), but not with either breast cancer laterality (p=.1906) or modality (BCT vs PMRT; p=.7487). Discussion: Long-term disease control and survival outcomes were better in BCT than PMRT patients, likely due to selection criteria. Cardiac events were associated with pretreatment heart disease, older age, and stage, suggesting that this population may benefit from advanced radiation techniques that can further limit cardiac dose. Neither breast cancer laterality nor treatment modality was associated with cardiac events. Citation Format: Smith TL, Mokhtech M, Bradley JA, Lightsey JL, Morris CG, Mendenhall NP. Can the risk of radiation-induced cardiac disease in breast cancer be mitigated with cardiac-sparing techniques? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-13.

Abstract P1-10-03: A randomized trial of accelerated breast radiotherapy utilizing either 3-dimensional radiotherapy versus intensity modulated radiotherapy

Abstract PURPOSE: Primary objective: patient self-assessment of breast pain between 3-dimensional radiotherapy (3D-CRT) versus intensity modulated radiotherapy (IMRT). Secondary objectives: breast cosmesis as well as local-regional recurrence and survival statistics. METHODS AND MATERIALS: 656 patients (3D-CRT n=325; IMRT n=331) were prospectively randomized to either IMRT or 3D-CRT accelerated partial breast radiotherapy to 38.5 Gy in 10 BID 3.85 Gy fractions. Follow-up was: 1, 4, 8, 12, 16, 20, 24 months then yearly. At follow-up, patients completed a cosmesis/pain self-assessment form and physicians completed a cosmesis and disease-status form. RESULTS: 636 patients completed treatment (3D-CRT n=316; IMRT n=320). Median age was 62. Mean tumor size was 1.1 cm. Mean margin was 7mm. Histology was: 74.5% IDCA, 7% ILCA, 17% DCIS, 0.5% Tubular, 1% Mucinous. 99% were ER+. HER2/neu status by IHC was 3+ in 16% of patients. Median follow-up is 2 years. Tables 1 and 2 show there is no significant difference in patient-assessed pain and cosmesis between the two treatment arms (p=0.14, =0.68 respectively). Decreasing pain and worsening cosmesis as reported by the patient were significantly related to time (p&amp;lt;0.01, =0.012 respectively). MD assessed cosmesis worsened significantly from baseline in the IMRT compared to 3D-CRT cohort (p=0.045). At 2 years Grade 3 and 4 toxicities were 1.5% and 3.9% respectively for 3D-CRT versus IMRT cohorts. Overall Survival at 2 years were 99.7% for both cohorts. There were 3/319 (0.9%) and 7/328 (2.1%) ipsilateral breast recurrences in the 3D-CRT and IMRT cohorts respectively. Patient breast pain by follow-up interval12 Months (3D n=167 and IMRT n=163)Rx ModalityNoneMildModerate-Severep value3D50.9%47.3%1.8%0.44IMRT52.1%44.2%3.7% 24 Months (3D n=111 and IMRT n=109)3D52.3%47.7% 0.07IMRT66.1%33.9% 36 Months (3D n=50 and IMRT n=34)3D60.0%40.0% 0.37IMRT58.8%41.2% 48 Months (3D n=12 and IMRT n=123D25.0%75.0% 0.19IMRT58.3%41.7% Results from mixed model for pain gradeEffectEstimateSELowerUpperp value3D vs IMRT0.0810.055-0.0260.1890.14Visit (Baseline, 12, 24, 36, 48 month-0.1010.019-0.137-0.064&amp;lt;0.01Table 1. Patient breast cosmesis by follow-up interval12 Months (3D n=162 and IMRT n=158)Rx ModalityNo changeSlight changeObvious changeDrastic changep value3D40.1%38.3%19.1%2.5%0.83IMRT41.8%40.5%15.2%2.5% 24 months (3D n=108 and IMRT n=108)3D38.9%40.7%18.5%1.9%0.30IMRT41.7%29.6%26.9%1.9% 36 Months (3D n=50 and IMRT n=34)3D38.0%34.0%28.0%0%0.37IMRT32.4%35.3%26.5%5.9% 48 Months (3D n=10 and IMRT n=12)3D10.0%30.0%60.0% 0.10IMRT50.0%8.3%41.7% Patient breast cosmoses by follow-up intervalEffectEstimateSELowerUpperp value3D vs IMRT0.0260.064-0.1000.1530.68All Visit (Baseline, 12, 24, 36, 48 month)-0.0530.021-0.095-0.0120.01Table 2. Conclusion: T here were no significant differences in patient-assessed pain and cosmesis between the two treatment arms (p=0.14, =0.68 respectively) and no significant increase in pain over time. However, MD assessed cosmesis showed worsening cosmesis in the IMRT cohort compared to the 3D-CRT cohort wen compared to baseline. Citation Format: Leonard CE, Sobus RD, Fryman S, Sedlacek S, Kercher J, Widner J, Asmar L, Wang Y, Howell K, Barke L, Carter D. A randomized trial of accelerated breast radiotherapy utilizing either 3-dimensional radiotherapy versus intensity modulated radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-03.

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma.

Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis.

Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china: A 25-year retrospective study.

Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC.A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients.Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location.Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients’ prognosis, which influenced LR control, DM control, and survival.

Retrorectal Epidermoid Cyst: A Rare Entity

Abstract Background: The presacral space, also known as the retrorectal space, is a potential space located anterior to the sacrum and coccyx and posterior to the rectum. This region contains the confluence of the embryologic hindgut, neuroectoderm, and the bony pelvis. As such, multiple different tissue types can give rise to retrorectal lesions. An epidermoid cyst is a kind of developmental cyst seen at this site. Case: This article presents the case of a young female diagnosed incidentally, during a gynecologic examination, with a palpable mass in the retrorectal space. Imaging findings supported the presence of a cystic tumor with a maximum diameter of 2 cm in the retrorectal space. The cyst was removed surgically. Results: Histopathologic examination revealed that the lesion was an epidermoid cyst. One year after surgery, the patient presented in good general condition; she was asymptomatic without clinical and imaging signs of any local–regional recurrence. Conclusions: As this tumor is rare in adul...

The Rationale for Post-Operative Radiation in Localized Bladder Cancer.

Local-regional recurrence for patients with ≥pT3 disease after radical cystectomy is a significant problem. Chemotherapy has not been shown to reduce the risk of local-regional recurrences in randomized prospective trials, and salvage therapies for local-regional failure are rarely successful. There is promising evidence, particularly from a recent Egyptian NCI trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared to chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the NCCN guidelines were revised in 2016 to include post-operative radiotherapy as an option to consider for patients with ≥pT3 disease. Despite advances in our understanding of the problem of local-regional failure after cystectomy and the potential role of adjuvant radiotherapy, the question of whether adjuvant radiotherapy should have a defined role for patients with locally advanced urothelial carcinoma has not yet been determined. The results of the NRG, European, Indian, and Egyptian trials on adjuvant radiotherapy are eagerly awaited. While none of these trials on their own may provide definitive conclusions, their aggregate outcomes will help clarify whether this treatment should have a role in the management of patients with locally advanced bladder cancer.

Post-mastectomy Radiotherapy for pT3N0 Breast Cancers: A Retrospective, Multi-Institution Review.

The role of post-mastectomy radiotherapy for pT3N0 breast cancers remains undefined. The purpose of this study was to report institutional outcomes for women with pT3N0 breast cancers treated with and without post-mastectomy radiotherapy. We collected data from two large tumor registries on pT3N0 breast cancers diagnosed between 1985 and 2014. Kaplan-Meier estimates were used to analyze freedom from local-regional recurrence (FFLR), relapse free survival, and overall survival. This analysis identified 93 women with pT3N0 breast cancers. Of these, 53 received post-mastectomy radiotherapy and 40 did not. Median follow-up was 6.2 years and 5.3 years in the non-post-mastectomy radiotherapy and post-mastectomy radiotherapy cohorts, respectively. Women not undergoing post-mastectomy radiotherapy were more likely to be diagnosed in the 1980s and 1990s and were less likely to receive systemic therapies than women receiving post-mastectomy radiotherapy (p < 0.05). There was a trend toward increased FFLR in the women receiving post-mastectomy radiotherapy (p = 0.15). FFLR in the post-mastectomy radiotherapy cohort was 98% at both 5 and 10 years. For women not receiving post-mastectomy radiotherapy, FFLR was 88% at both 5 and 10 years. Women not receiving post-mastectomy radiotherapy in our study had an isolated local-regional failure rate of 12% at 10 years, despite receiving inferior systemic treatment by current standards. Local-regional control after post-mastectomy radiotherapy for pT3N0 breast cancers was excellent. Further research is needed to define post-mastectomy radiotherapy indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.

Stereotactic Body Radiation Therapy in Octo- and Nonagenarians for the Treatment of Early-Stage Lung Cancer

To determine the safety and efficacy of lung stereotactic body radiation therapy (SBRT) in octo- and nonagenarians and to compare their outcomes with those of younger patients. Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5 institutions) database of 1083 cases. Details of patient factors, treatment specifics, toxicity, and clinical outcomes were extracted from the database. All events were calculated from the end of radiation therapy. Estimates of local recurrence, regional recurrence, and distant metastases were calculated using the competing risk method. Cause-specific survival (CSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcomes were compared for those aged <70, 70 to 79, and ≥80years. Univariable and multivariable analyses were performed to determine associations with CSS and OS in patients aged ≥80years. The median (range) follow-up was 1.7 (1-10) years, and median age was 75 (41-94) years. There were 305 patients aged <70years (28%), 448 aged 70 to 79years (41%), and 330 aged ≥80years (30%). There was no difference in 2-year local recurrence (4.2% vs 5.4% vs 3.7%, respectively, P=.7), regional recurrence (10.4% vs 7.8% vs 5.3%, P=.1), distant metastases (12.2% vs 7.7% vs 9.5%, P=.2), or CSS (90.6% vs 90.3% vs 90.4%, P=.6). Those aged ≥80years had significantly lower 2-year OS (73.6% vs 67.2% vs 63.3%, P<.01). The grade 3+pneumonitis rate was 1.3% versus 1.6% versus 1.5% (P=1.0) in patients aged <70, 70 to 79, and ≥80years, respectively. The 90-day mortality rates for patients aged <70, 70 to 79, and ≥80years were 1.3%, 2.5%, and 2.4% (P=.01), respectively. In patients aged ≥80years OS was associated with T category (hazard ratio 1.7; P<.01). Stereotactic body radiation therapy is a safe treatment modality in elderly patients (aged ≥80years). Despite larger tumor volumes, the tumor control outcomes were comparable to those in younger patients treated with SBRT. All patients with early-stage lung cancer, regardless of age, should be considered for treatment with SBRT.

P1.07-019 Large Cell Neuroendocrine Carcinoma of the Lung: Prognostic Factors of Survival and Recurrence after R0 Surgical Resection

Large cell neuroendocrine carcinomas (LCNEC) represent approximately 3% of all lung cancers. Due to this rarity, little knowledge exists about their outcome, prognosis or optimal treatment strategy. The objective of this study is to evaluate the outcomes of patients undergoing lung resection for LCNEC to identify the factors affecting survival and recurrence to help refine the optimal treatment strategy. We retrospectively reviewed 116 patients who underwent lung resection at 8 centers between 2000 and 2015. We excluded 18 patients: pNX(3), stage IV(5), R1-2(10). Univariate and multivariate analysis were performed to identify factors influencing disease-specific survival, overall survival and recurrence. The variables included age, gender, smoking habit, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, tumor location, tumor size, pT, pleura invasion, pN, pStage and neo/adjuvant treatments. Kaplan-Meier, Cox regression and ROC curve were used. A total of 98 patients (M/F:60/38) were analyzed with a median age of 66 years (IQR=58-72). Prior to resection, 11 (11%) received induction therapy. Resections included pneumonectomy (8), bilobectomy (3), lobectomy (76) and sublobar (11) with an associated lymph node sampling (N=52, 55%) and lymphadenectomy (N=43, 45%). Adjuvant therapy was delivered in 28 (30%). Pathologic stages were I (N=40, 41%), II (N=33, 34%) and IIIA (N=25, 25%). Median follow-up was 62 (IQR=19-120) months. The 5-year disease-specific and overall survival rates were 51.6% and 42.7%. On univariate analysis, pT was associated with disease-specific and overall survival (p=0.011, p=0.028). Similarly pT was also associated on multivariate analysis with disease-specific and overall survival (p=0.044, p=0.034). The recurrence rate was 55% (2% local, 10% regional, 32% systemic, 11% not-specified). The median disease-free interval was 16 (IQR=6-80) months. Local-regional recurrence wasn’t associated with any factor on univariate analysis. Systemic recurrence was correlated with tumor size (p=0.002), pT (p=0.003) and pStage (p=0.024) on univariate analysis. Tumor size was an independent prognostic factor of systemic recurrence on multivariate analysis (p=0.001) with a threshold value of 3 cm (AUC=0.712). The 5-year disease-free survival for systemic recurrence in tumors < 3 cm or ≥3 cm was 75.4% and 37.8% (p=0.001). The 5-year disease-specific survival was 56.7% and 47.3% (p=0.088). Treatment of LCNEC with predominately surgical resection results in a respectable 5-year survival. However, a high proportion of systemic recurrence occurs. Tumors ≥3 cm have a higher rate of systemic recurrence and lower rate of survival suggesting that adjuvant chemotherapy may be indicated for completely resected LCNEC ≥3 cm.

P2.02-003 Increased Circulating Cytokeratin-19 (Cyfra 21-1) is Predictive of Poor Outcome of Locally Advanced Squamous Cell Carcinoma in Lung

Our goal was to evaluate the prognostic significance of circulating tumor markers in locally advanced squamous cell carcinoma of lung (LA-SCCL). Eligible patients included those with histologically proven LA-SCCL, available baseline tumor marker panel analysis (carcino-embryonic antigen [CEA], carcinoma antigen 125 [CA125], squamous cell carcinoma antigen [SCC], cytokeratin-19 [Cyfra 21-1] and neuron-specific enolase [NSE]) and receiving definitive radiotherapy. Age, gender, radiation dose, baseline KPS, smoking history, weightless, TNM stage, PET staging, RT technique and treatment modality (radiotherapy alone vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy) were also retrospectively collected. To dichotomize the continuous values of tumor markers into categorical variables, ROC analysis was adopted to identify the optimal cutoff values using the progression within 2 years after diagnosis as the endpoint. Cox regression based multivariate analyses were used to select independent factors correlated with various survival endpoints. Overall survival (OS), local regional progression free survival (LRPFS) and distant metastasis free survival (DMFS) were defined as the time from diagnosis until the first occurrence of specific event: death, local-regional recurrence or distant metastasis, respectively. Progression free survival (PFS) was defined as the duration between the cancer diagnosis and the date of any progression or cancer related death. A total of 216 patients with LA-SCCL were analyzed. The optimal discriminative values for CEA, CA125, SCC, Cyfra 21-1 and NSE in predicting 2-y progression were 5.3 ng/ml, 17.0 U/ml, 2.5 ng/ml, 5.2 ng/ml and 17.8 ng/ml, respectively. Univariate analyses showed that increased Cyfra 21-1 was associated with inferior OS, LRPFS, DMFS and PFS. Increased NSE was predictive of poor OS, DMFS and PFS. CEA also presented significant correlation with OS. Under multivariate analysis involving all clinical and tumor markers, IIIA stage, better performance status, CEA ≤ 5.3 ng/ml and Cyfra 21-1 ≤ 5.2 ng/ml were independently associated with improved OS. IMRT technique, RT dose ≥ 60Gy and Cyfra 21-1 ≤ 5.2 ng/ml were correlated with better LRPFS. None-smoker, IIIA stage, NES ≤ 17.8 ng/ml were favorable predictors for DMFS. IIIA stage, KPS ≥ 80 and Cyfra 21-1 ≤ 5.2 ng/ml were advantageous factors related with favorable PFS. Baseline tumor marker panel including Cyfra 21-1, NSE and CEA can be prognostic of OS, local and distant tumor control for LA-SCCL, and should be recommended for baseline evaluation of tumor burden.

Pretreatment Nomograms for Local and Regional Recurrence after Radical Radiation Therapy for Primary Nasopharyngeal Carcinoma.

Background: The aim of this study was to build nomograms to predict local recurrence (LR) and regional recurrence (RR) in patients with nasopharyngeal carcinoma (NPC) underwent intensity-modulated radiation therapy (IMRT).Patients and Methods: A total of 1811 patients with non-metastatic NPC treated with IMRT (with or without chemotherapy) between October 2009 and February 2012 at our center were involved for building the nomograms. Nomograms for LR-free rate and RR-free rate at 3- and 5- year were generated as visualizations of Cox proportional hazards regression models, and validated using bootstrap resampling, estimating discrimination and calibration.Results: With a median follow up of 49.50 months, the 3- and 5- year LR-free rate were 95.43% and 94.30% respectively; the 3- and 5- year RR-free rate were 95.94% and 95.41% respectively. The final predictive model for LR included age, the neutrophil/leukocyte ratio (NWR), pathological type, primary gross tumor volume, maxillary sinus invasion, ethmoidal sinus invasion and lacerated foramen invasion; the model for RR involved NWR, plasma Epstein-Barr virus (EBV) DNA copy number, cervical lymph node volume and N category. The models showed fairly good discriminatory ability with concordance indices (c-indices) of 0.76 and 0.74 for predicting LR and RR, respectively, as well as good calibration. The proposed stratification of risk groups based on the nomograms allowed significant distinction between Kaplan-Meier curves for LR and RR.Conclusions: The proposed nomograms resulted in more-accurate prognostic prediction for LR and RR with a high concordance, hence to inform patients with high risk of recurrence on more aggressive therapy. The prognostic nomograms could better stratify patients into different risk groups.

Value of Radiology Modalities in Diagnosing Benign and Malignant Tumours of Breast: An Observational Study

Breast cancer is the most common malignant tumor among women. The objective of this research is to evaluate the specificity, sensitivity, and accuracy of BSGI, DC, and WE-MRI in the diagnosis of breast benign and malignant breast tumors. 228 female patients have participated in this observational research. The age was ranged from 31-68 years (mean age 42.37± 8.14 years) with suspicious breast lesions according to physical and imaging examination (mammography and/or ultrasonography). Moreover, women, who have suspected local regional recurrence after resection of malignant breast tumor and who were suspected to have tumor residual following chemotherapy or radiotherapy were also included. All patients underwent breast specific gamma imaging, DW-MRI, and DCE-MRI examination, and the results of breast MRI were compared with the histopathological results that were used as the standard diagnostic method. In this research, 111 women were found to have breast lesion. All breast lesions were undergone histopathological analysis using needle biopsy and/or excisional biopsy. Also, the results of the pathological analysis were correlated and confirmed with ultrasonography and mammography. The pathologic analysis confirmed that 76 (68.5%) of 111 lesions were benign breast lesions and 35 (31.5 %) of 111 were malignant breast lesions. The results proved that BSGI had the best results for the detection of breast lesions (sensitivity 96.7%, specificity 93.6 % and accuracy 94.8%) as compared with DCE-MRI (sensitivity 92.3%, specificity 85.6% and accuracy 88.2%) and diffusion weighted imaging (sensitivity 94.1%, specificity 88.5% and accuracy 91.4%). The research stated that BSGI is the most appropriate diagnostic tool for breast lesions.

External beam radiation and high-dose-rate brachytherapy for elderly patients with gastroesophageal junction adenocarcinoma.

PurposeThe aim of this study was to retrospectively observe and analyze the long-term treatment outcomes of 96 elderly patients with gastroesophageal junction adenocarcinoma (GEJAC) who were treated with californium-252 (252Cf) neutron brachytherapy (NBT) in combination with external beam radiotherapy (EBRT) with or without chemotherapy.Material and methodsFrom January 2002 to November 2012, 96 patients with GEJAC underwent treatment. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in 2 to 5 fractions, with 1 fraction per week. The total dose via EBRT was 40-54 Gy, which was delivered over a period of 4 to 5.5 weeks with normal fraction.ResultsThe median survival time for the 96 patients was 15.3 months, and the 1-, 2-, 3-, and 5-year rates of overall survival (OS) were 62.5%, 33.7%, 20.1%, and 7.9%, respectively. The 1-, 2-, 3-, and 5-year rates for local-regional control (LRC) were 78.7%, 57.9%, 41.8%, and 26.4%, respectively. The patients’ age was an independent factor that was significantly associated with OS (p = 0.006) and LRC (p = 0.0005), according to univariate analysis. The 3-year OS (LRC) was 31.9% (62.9%) for patients aged 70-74 years and 16.1% (19.5%) for patients aged ≥ 75 years. From the time of treatment completion to the development of local-regional recurrence or death, 5 (5.2%) patients experienced fistula and 7 (7.3%) experienced massive bleeding.ConclusionsThe clinical data indicated that NBT in combination with EBRT produced favorable local control and long-term survival rates for elderly patients with GEJAC, and that the side effects were tolerable. The patient’s age could be used to select the appropriate treatment in an elderly patient.