5-year Locoregional Control Research Articles

Failure patterns of head and neck squamous cell carcinoma treated with radical radiotherapy by intensity modulated radiotherapy technique using focal volume and dosimetric method.

Labeling locoregional failures in head and neck cancer (HNC) as "local" and "regional" becomes incomplete when treating with intensity modulated radiotherapy (IMRT). Target delineation and delivery errors, dose in-homogeneity complicate the assessment of failures. A combination of focal point and dosimetric method might attempt at simplifying failure analysis. One hundred eleven patients with locally advanced HNC treated with chemoradiation using IMRT were enrolled. Patients with documented failure had their recurrence volume assessed using focal point and dosimetric method. With a median follow-up of 20 (range 0-39) months and median locoregional control (LRC) of 30 (range 24.8-34.5) months, the patients had a 3-year overall survival and LRC of 70.6% and 48.9%, respectively. Of 39 failures, there were 69.2%, 7.6%, 5.1%, 12.8%, and 5.1% type A, B, C, D, and E, respectively using the focal point and dosimetric method. With the current classification, majority of the recurrences were high dose failures suggesting inherent radioresistance. While minority of failures were potentially preventable and needed modifying existing IMRT workflow.

Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity-modulated radiation therapy.

Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. p16/epidermal growth factor receptor (EGFR)/cluster of differentiation-44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. In the entire group and the p16 negative cohort, better 3-year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

High-dose versus standard-dose radiation therapy for cervical esophageal cancer: Retrospective single-institution study.

To evaluate the role of definitive radiotherapy using higher-than-standard-dose radiation of 50 Gy for carcinoma of the cervical esophagus (CCE). We reviewed 79 patients with stage I-III CCE, treated between 2000 and 2012. Patients received 5-fluorouracil/cisplatin-based chemotherapy concurrently and were divided into high-dose (≥59.4 Gy, n = 44) and standard-dose (<59.4 Gy, n = 35) groups. The median follow-up was 35 months for surviving patients. The high-dose group had significantly better 3-year local (90.0% vs 60.4%, P = .001) and locoregional (70.4% vs 45.3%, P = .04) control. Progression-free (45.4% vs 37.5%, P = .32) and overall (58.4% vs 49.1%, P = .69) survival rates were not different. High-dose radiation was an independent prognostic factor for locoregional control (P = .04). No differences in late toxicities (esophageal stenosis or tracheoesophageal fistula) were observed. High-dose radiation for CCE improves local and locoregional control, without increasing severe toxicities.

Compartmental surgery for oral tongue and floor of the mouth cancer: Oncologic outcomes.

Oral tongue/floor of mouth squamous cell carcinoma (OTFMSCC) with a depth of invasion (DOI) > 10 mm involves extrinsic muscles and lingual neurovascular/lymphatic bundles. "Compartmental" hemiglossopelvectomy (CHGP) was developed to improve loco-regional control by "en bloc" removal of tumor and its pathways of spread. We conducted a retrospective observational study on 45 CHGPs performed at a single institution for OTFMSCC with a DOI > 10 mm at CT/MR. Group A (n = 35) included naïve patients, and group B (n = 10) recurrent cancers. We evaluated 2-year overall survival (OS), disease-free survival (DFS), local control (LC), and loco-regional control (LRC). Two-year OS, DFS, LC, and LRC were 80%, 91%, 100%, and 94% for group A, and 27%, 26%, 67%, and 36% for group B, respectively. Salvage surgery and positive margins were significantly associated with worse prognosis. CHGP is a reliable oncologic approach in primary surgery for advanced OTFMSCC. In recurrent cancers, survival remains poor.

The efficacy of neutron radiation therapy in treating salivary gland malignancies

ObjectivesRadiation therapy is commonly used to treat head and neck malignancies. While there is abundant research regarding photon radiation therapy, literature on neutron radiotherapy (NRT) and oral complications is limited. This study aims to determine: (1) the 6-year and 10-year locoregional control and survival rates, (2) factors associated with locoregional control and survival and (3) the frequency of oral complications in patients undergoing NRT for salivary gland malignancies. Materials and methodsThis is a retrospective cohort study. The sample was composed of patients with salivary gland malignancies treated with NRT between 1997 and 2010. Data were extracted from patient charts, telephone surveys, and social security records. Multivariate competing risk and Cox regression models were used to assess predictors of locoregional control and survival. ResultsThe sample was composed of 545 subjects with a mean age of 54.2 years (±16). The predominant tumor and location were adenoid cystic carcinoma (47%) and the parotid (56%). Multivariate analysis indicated that positive surgical margins, biopsied/inoperable malignancies, neck involvement, and lymphovascular invasion were prognostic risk factors associated with decreased survival. The 6- and 10-year locoregional control rates were 84% and 79%. The 6- and 10-year survival rates were 72% and 62%. Osteoradionecrosis developed in 3.4% of subjects. ConclusionsThe 6- and 10-year locoregional control and survival rates compare favorably to rates reported for conventional photon radiation. Osteoradionecrosis rates were comparable to that of photon radiation treatment (2–7%). Given the potential benefits of NRT, healthcare professionals should be educated regarding its indications and oral complications.

Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults

ObjectivesThe natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger. Materials and methodsWe performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980–2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts. ResultsMedian patient age was 35 years (range, 19–40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001). ConclusionYoung adults with primary OC SCC may be treated with a similar treatment approach as older adults.

Risk-Based Optimization of Intensity-Modulated Radiation Therapy Guideline for Post-Operative Oral Cavity Cancer

To optimize previously established national intensity-modulated radiation therapy (IMRT) guideline for post-operative oral cavity squamous cell carcinoma (OSCC) in 2008, the follow-up results focusing on pattern and risk of failure were analyzed. Patients with OSCC treated with primary curative-intent surgery followed by postoperative IMRT according to the guideline with or without concurrent chemotherapy in our institute from 2010 to 2014 were retrospectively analyzed. Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox proportional hazard regression analyses were performed to identify predictors for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Locoregional recurrences (LRR) were reconstructed on the treatment planning computed tomography images by deformable image co-registration. Recurrences were classified as in-field, marginal or out-of-field if >95%, 20-95%, and <20% of the recurrence volume was within the 95% of the prescribed isodose, respectively. A total of 180 patients were enrolled in this study with a median follow-up of 49.6 months (range, 4.4-91.5 months). Among these patients, 133 (73.9%) remained disease-free during the follow-up period. There were 30 (16.7%) patients with LRR, 25 (13.9%) with distant metastasis, and 29 (16.1%) with second primary cancers. The 5-year LRC, DMFS, DFS, and OS were 82.6%, 73.3%, 67.6%, and 75.4%, respectively. On UVA, extracapsular extension (ECE) was the only factor significantly associated with poorer LRC (hazard ration, 2.49; 95% CI, 1.14-5.41; P = .022). On MVA, only pN2-3 was associated with worse DMFS (HR, 2.29; 95% CI, 1.02-5.15; P = .046), DFS (HR, 2.57; 95% CI, 1.18-5.56; P = .017), and OS (HR, 2.90; 95% CI, 1.13-7.45; P = .027). Of the 30 patients with LRR, 22 failed at the primary tumor site, 3 at the regional lymph nodes, and 5 at both the primary and lymph node areas. There were 28 LRR in high-risk planning target volume (PTV), 6 in intermediate-risk PTV, and 1 in low-risk PTV. Most LRR were in-field failures, except 11 marginal failures in high-risk PTV, and 1 in intermediate-risk PTV. Most common marginal failures occurred in infratemporal fossa (n=6) and ipsilateral parotid gland (n=4), all of which belonged to primary cancers originating from the buccal and gingival mucosa. Two out-of-field failures were noted over level VI neck and skin of the ipsilateral neck. The median time to LRR was 9.9 months (range, 2.0-68.2 months). The 5-year follow-up outcome of previous IMRT guideline for postoperative OSCC might be feasible for good LRC and OS. Factors such as ECE and pN2-3 warrant further consideration for intensified adjuvant therapy. The marginal recurrence rates in infratemporal fossa and ipsilateral parotid gland were relatively high in buccal and gingival cancers, indicating a need for more generous margin coverage of related spreading routes to further optimize the guideline.

Long Term Outcomes of a Positron Emission Tomography (PET) -Based Adaptive Radiation Therapy Protocol in Locally Advanced Head and Neck Cancer.

To report the long-term results of our PET-based adaptive head and neck cancer (HNC) protocol and to confirm outcomes/toxicities are not inferior to historic controls. In addition, we also report PET response parameters that are predictive of locoregional control (LRC). Patients with node positive HNC were eligible for the study. Patients underwent concurrent cisplatin or cetuximab treatment with radiation therapy (RT). The prescription dose was 70 Gy to the gross disease and 60 Gy to uninvolved nodal basins using a concomitant boost in 35 fractions. Simulation employed a thermoplastic mask on a PET-CT simulator and was repeated following fractions 10 and 22. Additionally, weekly PET-CT was obtained for response assessment. Plans were modified at those points taking into account reduction in disease burden and anatomical changes secondary to weight loss. The above protocol patients were matched 1:1 to non-protocol patients based on primary site, performance status, clinical T and N stage, smoking status, treatment dose/technique, chemotherapy use, and P16 status. The matched pairs were then analyzed to compare outcomes and toxicities between the two groups. In addition, the initial and weekly PET scans were analyzed for predictive correlation on LRC using 18FDG retention index (RI) and dose response matrix (DRM). The DRM represents a tumor’s SUV voxel response matrix to treatment. This can map out heterogeneity between and within individual neoplastic sites (either primary site or nodal disease) that may be more or less sensitive/resistant to treatment. A total of 37 patients were included on the adaptive protocol. Baseline characteristics were as follows: The median age was 63 years, 76% were oropharynx, 62% were cT1-2, 81% were cN2, 68% were smokers, and P16 was positive in 65% of patients. 3-year LRC, distant metastasis free survival, and overall survival were 81%, 75%, and 87%. The rates of chronic grade 3 toxicities were 8.1% for dysphagia and esophageal stricture and 2.7% for hoarseness and dental problems. There were 23 matched pairs generated and no significant difference in clinical disease outcomes was noted between the two groups. There was a significant decrease in chronic grade 2 xerostomia in the adaptive group vs the non-adaptive group (27% vs 70% p=0.017). Of interest, mean initial RI and the volume of DRM above certain thresholds were significant predictors of LRC on univariate analysis (p<0.05). Adaptive treatment for patients with locally advanced HNC resulted in significantly reduced rates of xerostomia relative to a matched cohort treated with non-adaptive treatment, and it did so without compromising disease control rates. RI and volume of DRM above certain thresholds are predictive for LRC and may be important factors in clarifying the optimal adaptive RT strategy for HNC in terms of both reducing treatment toxicity and potentially as a mid-treatment response parameter for adaptive dose painting in resistant tumors.

Rapid In-Field Failures Following Adjuvant Radiation for Buccal Squamous Cell Carcinoma

Squamous cell carcinoma originating in the buccal mucosa and retromolar trigone (RMT) have historically poor outcomes. Difficulties in discriminating tumor origin often result in these subsites being combined in surgical and pathological reports. We aimed to determine if making this anatomical distinction has implications for treatment design and clinical outcomes. Following institutional review board approval, we reviewed all of our oral cavity cases from the last 10 years and identified 27 tumors from either the buccal mucosa or RMT which underwent surgery with reconstruction followed by radiation therapy. We reviewed all pre-operative imaging and examination reports to accurately determine the site of origin. For patients who developed a local failure, we fused the pre-treatment imaging, simulation CT, and follow up imaging to determine the location of failures relative to the radiation field. All recurrences were biopsy proven. We used the Kaplan-meier method to calculate 2-year locoregional control and 2-year disease free survival. Patient characteristics can be found in table 1. The median prescribed radiation dose was 60 Gy and the median time from surgery to radiation was 50 (32-133) days. The 2-year locoregional control rates for buccal mucosa versus RMT respectively were 32.7% versus 68.4%. The 2-year disease free survival rates were 35.9% versus 68.4%. The median times to failure were 12.00 (4.9-115.0) months versus 18.5 (4.5-61.0) months. All buccal mucosa failures occurred within the high dose PTV with a median dose of 60 Gy within the failure region. Following locoregional failure 10 of the 12 patients have died, with a median time from local failure to death of 109 (4-529) days. Squamous cell carcinomas of the buccal mucosa have a dismal prognosis characterized by rapid in field failure. By contrast, RMT cancers may have more favorable outcomes. Therefore, differentiating tumor origin is important for prognostication and treatment. For buccal cancers, interval diagnostic imaging before radiation and treatment intensification should be explored.Abstract MO_6_2507; Table 1Patient CharacteristicsCharacteristicBuccal n=13 (%)RMT n=14 (%)Median Age (y)5857Male10 (77)12 (86)Female3 (23)2 (14)T stageT13 (23)2 (14)T24 (31)2 (14)T301 (7)T4a6 (46)8 (57)T4b01 (7)N stageN09 (69)5 (36)N12 (15)2 (14)N2a00N2b2 (15)7 (50)Overall StageI2 (15)0II4 (31)1 (7)III02 (14)IVA7 (54)10 (71)IVB01 (7)Positive Margin4 (31)8 (57)PNI4 (31)6 (43)LVSI1 (8)6 (43)ECE1 (8)5 (36)Chemo6 (46)7 (50)RT Dose (Median)6066 Open table in a new tab

Prognostic Significance of Pretreatment Primary Tumor and Nodal SUVmax on 18F-FDGPET/CT Imaging in Patients with Salivary Gland Carcinoma

To investigate the prognostic significance of primary tumor and nodal Fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in patients of salivary gland carcinoma (SGC) who have undergone curative treatment. This multicenter study retrospectively enrolled 117 SGC patients who had pretreatment 18F-FDG PET/CT and were treated with curative intent between 2004 and 2014. The most common histological subtypes were adenoid cystic carcinoma (N= 39, 34%), mucoepidermoid carcinoma (N = 28, 24%), and adenocarcinoma (N = 17,15%). Treatment outcomes were examined in relation to maximum standardized uptake values of the primary tumors (SUVmax-T) and positive-nodes (SUVmax-N) on pretreatment 18F-FDG PET/CT. After a median follow-up of 61 months, the 5-year locoregional control (LRC), regional control (RC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 78%, 87%, 67%, 62%, and 68%, respectively. The median SUVmax-T and SUVmax-N were 7.2 (range, 2.0−27.6) and 7.6 (range, 2.0−25.8), respectively. The optimal cutoff values of SUVmax-T and SUVmax-N which maximized the prognostic significance for PFS were both 7.0. Significantly lower 5-year LRC (P <0.001 and <0.001), DMFS (P <0.001 and <0.001), PFS (P <0.001 and <0.001) and OS (P <0.001 and <0.001) rates were observed in patients with SUVmax-T ≥7 and SUVmax-N ≥7, respectively. Multivariate analyses demonstrated that both SUVmax-T ≥7 and SUVmax-N ≥7 were significant independent predictors of LRC (P = 0.010 and 0.022), DMFS (P = 0.001 and 0.001), PFS (P <0.001 and = 0.007) and OS (P = 0.007 and 0.002), and SUVmax-N ≥7 significantly correlated with inferior RC (P <0.001). Subgroup analyses indicated that SUVmax-T predicted 5-year PFS in patients with adenoid cystic carcinoma (P = 0.006), mucoepidermoid carcinoma (P = 0.019), and adenocarcinoma (P = 0.041). Both pretreatment SUVmax-T and SUVmax-N on 18F-FDG PET/CT predicts treatment outcomes and survival in SGC patients treated with curative intent.

Integrated CT and 18F-FDG PET Based Radiomic Prediction Models for Pathological Response and Outcome in Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy and Esophagectomy

Pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose Positron Emission Tomography (PET) based radiomics exploratory analysis to investigate potential imaging biomarkers predictive of pathological response and clinical outcome in esophageal cancer patients treated with neoadjuvant chemo-radiotherapy (NACRT). Pre-treatment CT and PET images of 68 operable esophageal cancer patients treated with NACRT followed by esophagectomy were analyzed. A total of 126 features were extracted from the segmented primary disease individually from PET and CT images using an in-house algorithm. Radiomic features were compared with pathological response using tumor regression grade (TRG) and clinical parameters. Primary model were built using logistic regression, and similar models were also built and validated using random forest and libSVM methods. A composite feature-based signature formula, α PETf+ (1-α) CTf, where constant α (0<α<1) was optimized for each individual predictive model. Leave-one-out validation (LOOV) was performed. Locoregional control (LRC), recurrence free survival (RFS), metastasis free survival (MFS), and overall survival (OS) were estimated by Kaplan-Meier analysis and compared using log-rank test. Pathological complete response (pCR) was observed in 34 (50%) patients. Estimated actuarial 5-year RFS, LRC, MFS, and OS were 56.6% (mean: 67.8, 95% CI 53.7-81.8 months), 83.1% (mean: 92.8, 95% CI 81.4-104.2 months), 64.9% (mean: 76.4, 95% CI 62.2-90.7 months), 39.5% (median: 40, 95% CI 24.59-55.40), respectively. Near complete response (TRG 0-1) was associated with improved LRC [p = 0.04; Hazard Ratio (HR) 4.24 (1.01-19.01)]. Three separate predictive models were built for CT, PET, and combined CT+PET and analyzed separately for clinical endpoints. Integrated CT+PET features resulted in best predictive power. For pCR prediction, the signature used composite features with optimized α=0.8 resulted in AUC=0.87 and 76.5% accuracy in LOOV. For loco-regional recurrence, α=0.7, AUC=0.90 and 89.7% accuracy and for distant recurrence, α=0.4, AUC=0.83, and 83.8% accuracy in LOOV. For overall recurrence, α=0.5, AUC=0.80 and 73.5% accuracy in LOOV. For survival, α=0.7, AUC=0.85, accuracy 75% in LOOV. Stratifying patients by median radiomic signature predicted RFS: 80.1 vs. 40.1 months; 2-year RFS 77.4% vs. 52.6% (HR: 2.24 , 95% CI 1.01-5.58), respectively. The developed pre-treatment composite radiomic signatures were highly predictive of pCR, loco-regional recurrence, metastasis, and overall survival following NACRT plus esophagectomy. This is provocative data and further prospective validation study is in progress.

Long-Term Outcomes for Re-Irradiation of Recurrent Head-And-Neck Cancers: Mature Data from a Large Series

Locoregional recurrence or second-primary cancer in previously irradiated head-and-neck cancer patients poses a therapeutic challenge. Fractionated Stereotactic Body Radiotherapy (SBRT) should be considered in the multi-disciplinary approach for these patients. We report our mature results with reirradiation using fractionated SBRT for head-and-neck cancer with and without complete macroscopic resection. From 2002 to 2016, 133 lesions in 123 patients received robotic SBRT to the oropharynx (n = 21), hypopharynx (n = 8), nasopharynx (n = 9), paranasal sinus (n = 7), neck (n = 39), and other sites (n = 49) including overlapping sites. Ninety-two lesions in 88 patients were treated definitively, and 41 lesions were treated with palliative intent. Thirty-six percent of lesions underwent complete macroscopic resection before SBRT. Seventy-eight patients received chemosensitization. The median initial radiation dose was 70 Gy, and the median reirradiation SBRT dose was 30 Gy (21-42.5 Gy) in 2-5 fractions. Overall survival (OS) and locoregional control (LRC) were determined using the Kaplan Meier method. Cox regression analysis was used to determine predictors of LRC and OS. The median follow-up for surviving patients was 24.2 months following re-irradiation. Median OS for all patients was 12 months. For definitively treated patients, the 2-year OS and LRC rates were 42% and 36%, respectively. Durable local control was achieved in 56% of all patients. For these patients, median and 2-year OS were 24 months and 51%. Of those who were not a candidate for complete macroscopic resection, 54% achieved durable local control with radiotherapy. Median and 2-year OS were 15.8 months and 31%. Multivariate analysis demonstrated that higher total dose and surgical resection were significantly associated with improved LRC; durable local control and younger age were associated with improved OS. SBRT reirradiation for recurrent or second-primary head-and-neck cancer remains an important part of a multidisciplinary approach for these challenging cases. This study demonstrates encouraging response rates even in patients who are not ideal surgical candidates. The role of SBRT reirradiation in the era of immunotherapy utilization warrants further study.

Patterns of Failure and Clinical Outcomes of Post-operative Buccal Mucosa Cancers Treated with Ipsilateral Radiation Therapy

Loco-regional failure in carcinoma buccal mucosa (BM) after radical resection and adjuvant radiotherapy (RT) generally entails a bad prognosis. Usually, adjuvant RT (if indicated), is delivered to tumor bed and bilateral neck nodes. However, selected patients could be treated with ipsilateral RT to tumor bed and neck nodes (IL-RT). Literature on patterns of failure in this group of patients is sparse. We aimed to analyse the failure patterns and survival outcome in these cohort of patients treated at our institute. Eighty patients of post-operative BM cancers treated with IL-RT from June 2013 to May 2017 were included in this retrospective analysis. RT dose was 60-66 Gray in 30-33 fractions over 6-6.5 weeks delivered by linear accelerator using 3-dimensional conformal radiotherapy techniques. All outcomes were evaluated from the time of registration. Local, regional and loco-regional control was defined as time from registration to failure in tumor bed, regional nodes or both, respectively. Disease free survival (DFS) and overall survival (OS) were defined as time from registration to failure at any site (local, regional or distant) and death from any cause, respectively. Kaplan Meier method was used for all outcome analysis. The median age was 45.5 years (range 30-80). Patient characteristics are described in table 1. Median RT completion time and the overall treatment time were 6.2 weeks (range 5.9-7.1) and 11.6 weeks (range 8.5-19), respectively. 62 patients received 60 Gy, one patient 64 Gy and the rest received 66 Gy. The median follow-up time was 24.4 months (range 5-54.2).The 2-year local, regional and loco-regional control rates were 91.9%, 87.6% and 80.5%, respectively. The 2-year DFS and 2-year OS rates were 76.4% and 82.8%, respectively. The crude rates of failures at primary site, ipsilateral and contralateral neck were 12.5%, 12.5% and 3.7%, respectively. All patients with contralateral neck recurrence had N2 disease. Five patients (6.25%) had distant failures. Sixteen patients (20%) died of cancer and 2 patients died of non-malignant causes. The incidence of contralateral recurrence in BM cancer patients treated with primary surgery and adjuvant IL-RT is low. BM cancer with 1-3 risk factors may be treated with IL-RT, except, patients with N2 nodal status, who are at higher risk of contralateral regional recurrence.Abstract MO_23_2678; Table 1Patient CharacteristicsDistributionGender (Male: Female)75: 5T stage (T1: T2: T3: T4)10%: 43%: 26%: 21%N stage (N0: N1: N2)63%: 19%: 18%Overall TNM stage (I: II: III: IV) (As per AJCC 7th edition)5%: 30%: 23%: 42%Risk factors for post-operative RT (>pT3: pN+: PNI: LVI: Close margins: Tumor thickness)*52: 40: 18: 24: 13: 55Number of risk factors for post-op RT (1: 2: 3: >4)10%: 60%: 17.5%: 12.5%Grade (1: 2: 3)42: 34: 4*The total may not add up to 100% because of presence of multiple factors. Abbreviations: RT=Radiotherapy; PNI=Peri-neural invasion; LVI=Lympho-vascular invasion Open table in a new tab

Post-Radiation Immunosuppression is Associated with Poor Clinical Outcomes in HPV-negative Oropharyngeal Cancers

An elevated neutrophil to lymphocyte ratio (NLR) in the peripheral blood has been associated with poor disease outcomes in a number of solid tumors sites. However, the prognostic value of NLR in human papilloma virus (HPV)-negative oropharyngeal cancers (OPCs) remains controversial. We hypothesized that post-radiation lymphopenia and NLR would be associated with patient outcomes. HPV-negative oropharyngeal cancer patients treated with radiation therapy at an academic center from 1997-2013 were queried from a prospectively maintained database. Absolute lymphocyte counts (ALC) and absolute neutrophil counts (ANC) were evaluated before treatment, at the lymphocyte count nadir during treatment, 3 months, 6 months, and 12 months after radiation (RT) start. Logistic regression was used to determine clinical and treatment-related predictors of lymphopenia. Kaplan-Meier and Cox analyses were done for loco-regional control (LRC), progression free survival (PFS), and overall survival (OS). We identified 108 patients with HPV-negative oropharyngeal cancers, of whom 57 received surgery followed by post-operative radiation (PORT) and 51 received definitive RT. Median radiation dose was 70Gy for definitive RT and 66Gy for PORT. Median follow up was 37 months (range 2-197). During treatment, 85% of patients developed grade ≥ 3 lymphopenia and 22% with grade 4 lymphopenia, with no difference in lymphopenia rates between patients receiving PORT and those receiving definitive RT. Stage T3-4 tumor vs. T1-2 (OR = 5.3, 95% CI 1.4-20, p = 0.015) was the only clinical factor associated with developing grade 4 lymphopenia. Chemotherapy and surgery did not significantly associate with grade ≥ 3 lymphopenia at any timepoint. Pre-treatment and treatment nadir blood counts were not associated with OS. Three months after RT start, 19 (29%) out of 65 patients with blood counts had grade ≥ 3 lymphopenia. The estimated 3-year LRC, PFS, and OS in patients with and without grade ≥ 3 lymphopenia at 3 months after RT was 73% vs. 82% (p = 0.334), 36% vs. 63% (p = 0.014), and 34% vs. 64% (p = 0.016), respectively. In multivariable analysis, definitive radiation (HR = 3.2, 95% CI 1.5-6.7) and grade ≥ 3 lymphopenia (HR =2.5, 95% CI 1.3-5.0) at 3 months after RT were associated with worse OS. Lymphopenia and NLR as early as 3 months post-radiation associate with poor clinical outcomes in HPV-negative oropharyngeal cancer patients. Validation in a prospective clinical trial is warranted.

Adjuvant Radiation Therapy for Vulvar Squamous Cell Carcinoma: Does p16-Positivity Influence Locoregional Control?

Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus (HPV) has been implicated as a causative factor for a subset of these patients. The purpose of this study is to evaluate if p16-positivity, which is surrogate for HPV infection, predicts for better response rates and survival in women who undergo surgery followed by adjuvant radiation therapy (RT). A retrospective chart review was undertaken of all women treated with adjuvant radiation therapy from 2000-2016 for VSCC at our institution. Available tissue blocks were stained for p16. Each tumor was assigned an H-score according to the College of American Pathologists criteria. P16-positivity was defined as diffuse, strong immunoreactivity within invasive tumor with an H-score of 200+. P16 +/- groups were compared using Chi-squared and t-test. These were correlated with outcomes via Kaplan-Meier with log-rank technique. Time to an event was defined as the time from completion of RT. Thirty-nine women were identified. Median follow up was 25.6 months and 43.3 months for living patients. Ten women (25.6%) had p16+ pathology. The median age at diagnosis was 59.3 years for women with p16+ tumors and 70.2 years for women with p16- tumors (p=0.04). The distribution of stage did not differ by p16-status. The median maximal vulvar dose was 54.4Gy (range: 42.6-63.0Gy). The indication for adjuvant RT was close/positive margins in 19 women (48.7%), positive nodes in 8 (20.5%), and both in 12 (30.8%). The average pathologic tumor size was 2.1cm for p16+ tumors and 3.4cm for p16- tumors (p=0.028). Average margin size was not statistically different. There was a trend towards differences in the average number of pathologically involved lymph nodes, 0.5 vs 1.26 for p16+ vs p16-, p=0.077. Vulvar control rates differed by p16 status at 2 years: 88.9% vs 52.3% for p16+ vs p16-, p=0.041. This translated to a strong trend in differences in two-year locoregional control as well: 77.8% vs 47.4% for p16+ vs p16-, respectively, p=0.064. In women with only one indication for adjuvant RT, this benefit was more pronounced for women with p16+ tumors vs p16-: 2-year locoregional control 100% vs 48.5%, p=0.041. Two-year overall survival was not significantly different between p16+/- cohorts (88.9% vs 64.6%, p=0.405). Survival was impacted by risk factors necessitating adjuvant RT, however. Women with either close/positive margins or positive nodes had a 2-year survival of 80.4% vs 50.0% for women with both risk factors (p=0.044). p16+/- status did not statistically influence survival for women with one risk factor, but survival was numerically different at 2 years (100% vs 73.2%). The p16 positivity appears to be a prognostic factor for locoregional control rates in VSCC treated with vulvectomy and adjuvant radiation therapy for close/positive margins or positive lymph nodes. This benefit was pronounced especially in women with only close/positive margins or positive lymph nodes.

Treatment outcomes of unknown primary squamous cell carcinoma of the head and neck.

BackgroundTreatment modality of unknown primary squamous cell carcinoma of the head and neck (SCCHN) remains controversial.ObjectivesTo evaluate the treatment outcomes and prognostic factors of unknown primary SCCHN.Materials and methodsPatients with unknown primary SCCHN from April 1995 to March 2013 were recruited retrospectively.ResultsSixty-nine patients were enrolled. The median time of follow-up was 55.5 months. The 2-year loco-regional control rate of all the patients was 60.4%. Multivariate Cox regression analysis revealed that N3 stage, extracapsular spread, distant metastasis, and treatment modality were significantly associated with neck recurrence. The actuarial 5-year disease-specific survival rates of neck dissection, neck dissection plus adjuvant therapy, radiotherapy alone, and combined therapy were 80.0%, 61.7%, 33.3%, and 68.8%, respectively (p = 0.046). The 5-year disease-specific survival rates of N1/N2a, N2b/N2c, and N3 stage were 83.9%, 64.3%, and 36.7%, respectively (p = 0.013). Univariate regression analysis revealed that neck recurrence, supraclavicular node involvement, distant metastasis, N3 stage, and unhealthy lifestyle habits were correlated with disease-specific mortality, especially the first three parameters. Patient’s occupation and comorbidity were not significantly correlated with survival.ConclusionsComposite therapy is mandatory for advanced unknown primary SCCHN. Supraclavicular node involvement and unhealthy lifestyle habits, such as betel nut chewing, indicate a poor prognosis.

Outcomes Following Salvage Radiation and Systemic Therapy for Isolated Locoregional Recurrence of Breast Cancer after Mastectomy: Impact of Constructed Biologic Subtype.

Purpose This study examines factors associated with outcomes following salvage radiation and systemic therapy for breast cancer patients who developed isolated locoregional recurrence (ILRR) after mastectomy alone, while focusing on the prognostic significance of constructed biologic subtype in this setting. Methods and Materials 269 postmastectomy patients in total treated for ILRR were included. Cumulative incidence of locoregional control (LRC), distant metastasis (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated using Kaplan-Meier method. For statistical analysis, biologic subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic-pathological and treatment-related parameters with outcomes was evaluated using a Cox regression model. Results At a median follow-up of 65 months, 56 (20.8%) patients failed to secure LRC after radiotherapy, and 165 patients (61.3%) developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was 77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that constructed biologic subtype represented the most significant prognostic factor for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec-/HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P < 0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28, P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus 22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no radical surgery and involved field irradiation alone, whereas factors associated with poor survivals included positive nodes at primary diagnosis and regional recurrence. Conclusions Constructed biologic subtypes remained to be predictive of both disease control and survivals after salvage radiation for postmastectomy ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of locoregional failure and subsequent DM and tended to have worse survivals despite salvage therapies.

Compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin concurrent chemoradiation in locally advanced head and neck cancer

AbstractAimWeekly low-dose cisplatin is routinely used in concurrent chemoradiation (CCRT) in locally advanced head and neck cancer (LAHNC), despite 3-weekly cisplatin being the standard of care. We compared compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin CCRT in LAHNC.Materials and methodsIn this retrospective study, weekly cisplatin 50 mg flat dose was compared with 3-weekly cisplatin 100 mg/m2, when given in CCRT in LAHNC with curative intent. The study outcome was compliance, toxicity, loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS).ResultsEighty-four patients received CCRT from January 2013 to June 2017, 40 in weekly and 44 in 3-weekly arm. There was no difference between the arms not completing scheduled radiation therapy or chemotherapy. Patient receiving 200 mg/m2 cisplatin is higher in 3-weekly arm compared with weekly arm (75 versus 40·9%; p&lt;0·0015). Compared with 3-weekly arm, more patient in weekly arm developed grade ≥3 mucositis (52·5 versus 15·9%, p=0·0004), day care intravenous hydration (82·5 versus 38·6% &lt;0·0001) and in-patient admission (55·0 versus 18·2%; p=0·0004). The 2-year LRC, DFS and OS in weekly versus 3-weekly arm were: 70 versus 61·4% (p=0·406); 67·5 versus 56·8% (p=0·314); 67·5 versus 61·4% (p=0·558), respectively. The median time to LRR, DFs and OS was not reached.ConclusionsWeekly cisplatin is comparable with 3-weekly cisplatin in terms of compliance, disease control and survival, but with increased grade 3 mucositis and higher admissions for supportive care.

Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16)

BackgroundGiven the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status. Patients and MethodsWe analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses. ResultsIn all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P = .023) and DFS (P = .001). Age ≥ 50 years (P = .027), negative resection margin (P = .002), and axillary lymph node dissection (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups. ConclusionIn ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials.

Long-term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors.

We observed high survival in a previous report of a p16-positive, oropharyngeal carcinoma (OPC) cohort treated primarily with transoral laser microsurgery (TLM) ± adjuvant therapy and followed for ≥ 12 months. To address long-term outcomes of primary transoral surgery for this unique disease, we present an updated analysis of our cohort with extended follow-up. A prospectively assembled TLM cohort of 171 OPC patients was analyzed for disease-free, disease-specific, and overall survival (disease-free survival [DFS], disease-specific survival [DSS], overall survival [OS]) and functional outcomes, with a minimum follow-up of 60 months or to death. Median follow-up was 103 (60-201) months. Five-year DFS, DSS, and OS estimates were 85% (95% confidence interval [CI]: 80%-91%), 93% (95% CI: 89%-97%), and 90% (95% CI: 86%-95%). Recurrence occurred in 20 (12%; 7 locoregional, 13 distant); median time to recurrence was 18.8 months; and 90% occurred within 48 months. Age, smoking, American Joint Committee on Cancer 8th edition clinical tumor-category, pathologic tumor (pT)-category, pathologic tumor-node-metastasis (pTNM), and any adjuvant were significantly associated with disease-free survival in multivariable analyses, whereas pT-category, pN-category, TNM grouping, and angioinvasion were associated with DSS. A second primary developed in six (3.5%) patients. Indications for gastrostomy were recurrence/second primary (11), postadjuvant esophageal stenosis (6), comorbidities (3), and osteo/chondroradionecrosis (3); only seven (4%) had a gastrostomy tube in the absence of these factors, all of whom received adjuvant therapy. Two had a tracheostomy tube [chondoradionecrosis (1), recurrence (1)]. High 5-year survival and locoregional control were observed, with recurrence occurring more commonly as distant metastasis. The observed time to recurrence suggests posttreatment oncologic surveillance for at least 48 months. Identified prognosticators will inform adjuvant treatment considerations, trial planning, and patient counseling for long-term outcomes. Laryngoscope, 2018 LEVEL OF EVIDENCE: 2b Laryngoscope, 129:1141-1149, 2019.