Regional Relapse Research Articles

Characteristics and Treatment Outcomes of Primary Mediastinal Seminomas: A Report of 30 Cases from a Single Center

The low incidence primary mediastinal seminoma has precluded the development of clinical trials, and present knowledge is based on case reports and tiny studies. We performed this single-center retrospective analysis to evaluate the clinical characteristics, treatments, and prognosis in patients with pathologically confirmed primary mediastinal seminoma. Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected from 30 patients who attended our institution between December 2000 and December 2018. Survival was assessed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. The 30 patients were with a median age of 30 years old (13-63 years). Chest pain, stuffiness and cough were the most common symptoms (22.2%,22.2%, 13.9%). The medium maximum diameter of primary tumor was 10.2 centimeters. Eighteen patients were with invasion of adjacent structures such as lung and superior vena vessel. Three and two patients were diagnosed as lymph node metastasis and distant metastasis. R0 resection and debulking resection were performed in 12(40.0%) and 2(6.7%) patients, respectively. Treatment comprised radiotherapy in 15(50.0%) patients and chemotherapy in 27(90.0%). The median radiation dose was 45Gy and the most widely used chemotherapy regimens were bleomycin, etoposide and cisplatin. The median follow-up time was 25.1months(1.8 -198.2 months). At the last follow up, two patients died. Both two patients lived more than ten years after treatment and neither of them died of seminomas or treatment induced toxicities. Local recurrence and distant metastasis were observed in 3 patients each. At 5 years and 10 years, local-regional relapse free survivals were 86.7% and 86.7%, overall survivals were 100% and 100%, progression-free survivals were77.4% and 77.4%, and distant metastasis–free survivals were 85.6% and 85.6%, respectively. In univariate analysis, there is a marginal differences of local regional relapse free survival between patients who received radiotherapy and who did not (100% vs. 74.3%, p=0.081). Primary mediastinal seminoma was frequently diagnosed with invasion of adjacent structures. Chemotherapy is the most widely used treatment and radiotherapy may increase local-regional relapse free survival.

Accelerated partial-breast irradiation with high-dose-rate brachytherapy: Mature results of a Phase II trial

PurposeThe purpose of this study was to report mature clinical and cosmetic results of accelerated partial-breast irradiation with interstitial multicatheter high-dose-rate brachytherapy (HDR-BRT) in patients with early breast cancer. Methods and Materials133 patients were recruited in a Phase II trial of exclusive HDR-BRT. Inclusion criteria were age ≥40 years, PS 0–2, unifocal invasive ductal cancer, intraductal cancer component <25%, negative axillary nodes, and tumor size ≤2.5 cm. Treatment schedule was 4 Gy twice a day up to a total dose of 32 Gy in eight fractions. ResultsMedian age was 67 years (range, 42–85). There were 7 (5%) pT1a, 48 (36%) pT1b, 72 (54%) pT1c, and 6 (5%) pT2. Estrogen and progesterone receptors were positive in 119 (89%) and 93 (70%) patients, respectively. The median followup was 110 months (range, 12–163). After HDR-BRT, there were 3 (2%) in-field breast recurrences and 1 (1%) out-field breast recurrence. 5 (4%) patients developed contralateral breast cancer, another one (1%) isolated regional relapse in axillary node and 3 (2%) distant progression of disease. 19 (14%) patients reported a second primary cancer. 5-, 10-, and 13-year overall survival and cancer-specific survival were 95% and 100%, 84.5% and 100%, and 81.4% and 100%, respectively. Cosmetic outcome was excellent in 80% of cases. Late toxicity was significantly related to the skin administered doses (≤55% vs. > 55% of the prescribed dose, p < 0.05). ConclusionsAccelerated partial-breast irradiation delivered with HDR-BRT in selected patients with breast cancer was associated to high local control and survival with excellent cosmetic outcomes overall when skin dose was ≤55%.

Surgery or Radiotherapy of the Primary Tumor in T1-2 Head and Neck Squamous Cell Carcinoma with Resectable N3 Nodes: A Multicenter GETTEC Study.

The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1-2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease. This retrospective multicentric Groupe d'Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage. Of 189 T1-2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary. In patients with T1-2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.

Abstract 737: NF-κB pathway activation by clonal mutations contributes to the recurrence of nasopharyngeal carcinoma

Abstract Objectives: Identification and characterization of the genomic features that potentially drive NPC recurrence. Methods: We performed whole-genome/whole-exome sequencing of fresh tumors and corresponding blood samples from 55 rNPC and 44 pNPC patients. Additionally, previously published pNPC exome data were integrated for analysis. Immunohistochemistry and histologic analyses were performed to identify novel biomarkers among the differential mutational events between pNPC and rNPC in independent cohorts of 148 rNPC and 237 pNPC samples with complete clinical follow-up. Results: rNPC and pNPC tissues had similar mutational burdens; however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD and NFKBIA were all clonal in rNPC; however, 55.6-57.9% of them were clonal in pNPC (P &amp;lt; 0.05). In general, the number of clonal mutations in NF-κB pathway-associated genes was significantly higher in rNPC than in pNPC (P &amp;lt; 0.05). Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with local regional relapse than in those without relapse (P = 0.006). Further, in both the pNPC training and validation cohorts, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival (LRRFS) in pNPC. Accordingly, concurrent chemotherapy for patients with high nuclear NF-κB reduced the rate of locoregional relapse. Lastly, we functionally validated that inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in NPC cells, strongly supporting our in vivo results. Conclusion: NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting LRRFS and suggesting treatment for pNPC patients. Finally, blocking NF-κB activity may be a novel and effective therapeutic modality for treating NPC. Citation Format: Rui You, You-Ping Liu, Ming-Yuan Chen. NF-κB pathway activation by clonal mutations contributes to the recurrence of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 737.

A review of the influence of mammographic density on breast cancer clinical and pathological phenotype.

It is well established that high mammographic density (MD), when adjusted for age and body mass index, is one of the strongest known risk factors for breast cancer (BC), and also associates with higher incidence of interval cancers in screening due to the masking of early mammographic abnormalities. Increasing research is being undertaken to determine the underlying histological and biochemical determinants of MD and their consequences for BC pathogenesis, anticipating that improved mechanistic insights may lead to novel preventative or treatment interventions. At the same time, technological advances in digital and contrast mammography are such that the validity of well-established relationships needs to be re-examined in this context. With attention to old versus new technologies, we conducted a literature review to summarise the relationships between clinicopathologic features of BC and the density of the surrounding breast tissue on mammography, including the associations with BC biological features inclusive of subtype, and implications for the clinical disease course encompassing relapse, progression, treatment response and survival. There is reasonable evidence to support positive relationships between high MD (HMD) and tumour size, lymph node positivity and local relapse in the absence of radiotherapy, but not between HMD and LVI, regional relapse or distant metastasis. Conflicting data exist for associations of HMD with tumour location, grade, intrinsic subtype, receptor status, second primary incidence and survival, which need further confirmatory studies. We did not identify any relationships that did not hold up when data involving newer imaging techniques were employed in analysis.

ONCOLOGICAL SAFETY OF RADICAL SUBCUTANEOUS/ SKIN-SPARING MASTECTOMIES WITH SIMULTANEOUS RECONSTRUCTION IN CANCER

The article analyzes 472 patients diagnosed with breast cancer (breast cancer) who underwent radical subcutaneous/ skin-sparing mastectomy in combined or complex treatment. In the Department of Oncology and reconstructive plastic surgery of breast and skin mnioi them.P. A. Herzen radical skin-sparing mastectomy was performed in 255 (54.1 %) and radical subcutaneous mastectomy in 217 (45.9 %) patients. Reconstruction was carried out by autotissues, expander, followed by replacement with an endoprosthesis, as well as a combination of patches and endoprostheses. The mean age of patients was 43.8±2.2 (18-73) years. 11 (2,3±0,7 %) patients were diagnosed with relapse of breast cancer, while in 6 cases local and in 5 cases regional relapse (metastases in subclavian lymph nodes). Treatment of recurrences of breast cancer was as follows: in two cases, polychemotherapy courses were conducted, in 8 operations were performed - excision of relapse in the breast (3) and subclavian lymphadenectomy (2), removal of the reconstructed gland (3), in 1 case - radiation therapy. In 13 % recurrences of breast cancer were diagnosed at stage III OF breast cancer, the lowest percentage of relapse was 1.4 % at stage I. In luminal type A, recurrence of breast cancer was diagnosed in 1.8 %, in luminal B in 3.6 %, in triple negative type - 2.5 %, in luminal In Neg2 positive - 4.1 %. Metastases of breast cancer in our group of patients were diagnosed in 26 (5.5±1 %) patients. The highest percentage of long-term metastasis in our study revealed - 12.5 % at stage III, the lowest percentage of 3.4 at stage I breast cancer. 3-year overall survival of breast cancer patients in our group was 97.4 % (n=269).

A safety study of nivolumab in patients with recurrent and/or metastatic platinum-refractory squamous cell carcinoma of the head and neck (R/M SCCHN): Interim analysis on 199 patients—The TOPNIVO study on behalf of the GORTEC and the Unicancer Head &amp; Neck Group.

6032 Background: In the randomized phase III Study CA209141, Nivolumab (N) demonstrated significant overall survival (OS) benefit with favorable safety profile for platinum refractory R/M SCCHN and is now approved for these patients (pts). The objectives of the study are to provide additional insight into the frequency of high-grade AEs related to N and the efficacy of N in real life. Methods: Between August and December 2017, 203 pts were included in the multicenter, non-controlled phase II TOPNIVO. The main inclusion criteria were patients with platinum refractory R/M SCCHN with progressive disease, ECOG 0-2. Pts received N 3mg/kg every 2 weeks intravenously over 30 minutes. Four pts did not receive N. We report here the safety during the first 6 months (mo) after inclusion and OS results on the first 199 treated pts. Results: Median age was 62 yr, 83% were male, 84% were ECOG 0-1, 16% 2. The primary site of cancer was oral cavity 26%, oropharynx 38%, larynx 16%, hypopharynx 21%. 33% had loco regional relapse, 32% metastatic disease and 35% both. 49% had received one prior line of chemotherapy and 30% two prior lines. 157 (79%) pts ended their treatment within the first six mo: 5 for AE related to N (pneumonitis 3 pts, hepatitis 1 pt, diarrhea 1 pt), 107 for progression, 33 for death (24 related to progression, 9 to intercurrent disease), 12 other. 132 pts (66%) experienced at least 1 AE grade ≥3. On the 226 AEs grade 3-4, 21 (mainly pneumopathy, lipase increase and asthenia) were related to N and occurred in 18 pts. On the 51 AEs grade 5, 3 were considered related to N (2 pneumonitis, 1 cardiac arrest). The median OS was 7.7 mo (CI 95% [6.0; 9.5]) in the whole population; 9.2 mo [6.8; 12.1] in the 167 pts with ECOG 0-1, 3.0 mo [1.1; 6.0] in the 32 pts with ECOG 2; 12.1 mo [7.6; NR] in the 64 pts with metastatic disease, 7.7 mo [5.0; 9.6] in the 66 pts with locoregional disease and 4.6 mo [3.1; 7.9] in the 69 pts with both. OS was similar in pts older or younger 70 yr. Conclusions: The interim analysis of the TOPNIVO study shows no additional toxicities of N compared to what has been described previously, confirms the previous results of OS and provides new survival data in subgroups of pts. Clinical trial information: NCT03226756.

Wide local excision prior to sentinel lymph node biopsy for primary melanoma of the head and neck.

Previous wide local excision prior to sentinel lymph node biopsy (SLNB) may have the potential to disrupt lymphatic channels, thus incorrectly identifying the sentinel node. The purpose of this study was to investigate: (1) regional recurrence rates of prior wide local excision compared to other biopsy techniques and (2) survival outcomes in patients with melanoma of the head and neck. Between the years 2000 and 2016, 391 cases were reviewed with a median follow-up time of 30 months in a large tertiary care center. Biopsy practices included shave, punch, wide local excision, and narrow margin excisional/Mohs, and associations with time to local or regional relapse and death from melanoma were evaluated. Main outcomes included identification of sentinel lymph nodes, overall survival, and melanoma-specific survival. Of the 391 patients, biopsy patterns were as follows: 77 (19%) unknown biopsy, 30 (8%) prior wide local excision (WLE), 105 (27%) narrow margin excisional biopsy, 69 (18%) punch biopsy, and 110 (28%) shave biopsy. SLNB was successfully identified in all 30 patients whom had a prior WLE. There were 50 regional recurrences in the neck and 27 local recurrences with the median (IQR) at 1.2 years and 1.0 years, respectively. Multivariable associations of type of prior biopsy, depth of invasion, and nodal status with time to regional recurrence, local recurrence, overall survival, and melanoma-specific survival were not significantly different. Sentinel lymph node biopsy for melanoma of the head and neck can be successfully performed in patients after previous wide local excision.

EP-1592 Consolidative radiotherapy after loco regional relapse in muscle invasive bladder cancer

EP-1592 Consolidative radiotherapy after loco regional relapse in muscle invasive bladder cancer

Maximum standardized uptake value at pre-treatment PET in estimating lung cancer progression after stereotactic body radiotherapy.

PurposeThis study aimed to identify the feasibility of the maximum standardized uptake value (SUVmax) on baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) as a predictive factor for prognosis in early stage primary lung cancer treated with stereotactic body radiotherapy (SBRT).Materials and MethodsTwenty-seven T1-3N0M0 primary lung cancer patients treated with curative SBRT between 2010 and 2018 were retrospectively evaluated. Four patients (14.8%) treated with SBRT to address residual tumor after wedge resection and one patient (3.7%) with local recurrence after resection were included. The SUVmax at baseline PET/CT was assessed to determine its relationship with prognosis after SBRT. Patients were divided into two groups based on maximum SUVmax on pre-treatment FDG PET/CT, estimated by receiver operating characteristic curve.ResultsThe median follow-up period was 17.7 months (range, 2.3 to 60.0 months). The actuarial 2-year local control, progressionfree survival (PFS), and overall survival were 80.4%, 66.0%, and 78.2%, respectively. With regard to failure patterns, 5 patients exhibited local failure (in-field failure, 18.5%), 1 (3.7%) experienced regional nodal relapse, and other 2 (7.4%) developed distant failure. SUVmax was significantly correlated with progression (p = 0.08, optimal cut-off point SUVmax > 5.1). PFS was significantly influenced by pretreatment SUVmax (SUVmax > 5.1 vs. SUVmax ≤ 5.1; p = 0.012) and T stage (T1 vs. T2-3; p = 0.012).ConclusionSUVmax at pre-treatment FDG PET/CT demonstrated a predictive value for PFS after SBRT for lung cancer.

Neck management in head and neck squamous cell carcinomas: where do we stand?

Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/- followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms 'neck management' OR 'cervical lymphadenopathies' AND 'head and neck neoplasms'. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV- or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna's trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers' experience, in the context of limited data, especially for N2-3 HPV- HNSCC.

Evaluation of the Patient Profile and Current Pattern of Care with Docetaxel Based Adjuvant Regimen in Operable Breast Cancer

Background: Early stage breast cancer can often be cured with surgery alone though there are chances of recurrent disease and decrease in survival. Adjuvant poly-chemotherapy with docetaxel-based regimens can improve both disease-free and overall survival in patients with operable breast cancer.&#x0D; Objective: This study was designed to evaluate the patient profile and current pattern of care with docetaxel based adjuvant regimen in operable breast cancer patients including the treatment outcome from clinical practice.&#x0D; Materials and method: This prospective, observational, non-comparative study planned to enroll newly diagnosed operable breast cancer patients with high risk of recurrence after surgery. Selection of docetaxel-based treatment strategy and dosage of therapy was at the discretion of individual oncologists as per routine clinical practice. Patient data were recorded during inclusion, each cycle of therapy, and follow-up at 1 year (+/- 1 month) after inclusion.&#x0D; Results: Between August 2008 and July 2011 a total of 85 patients with median age of 53 years (23-73 years) were enrolled and 53 (62.4%) patients were postmenopausal. Ductal carcinoma, the most common cancer type,was found in 73 (85.9%) patients. Receptor status was positive for estrogen, progesterone or Her2/neu/erbB2 in 65.9%, 47.1% and 5.8% patients, respectively. Mastectomy either partial or total was performed in 76 (89.4%) patients for the current disease. An average of 8 (range: 2-15) lymph nodes (LN) mostly in axilla were excised in 56 patients and average of 4 (range: 1-11) LN nodes were positive. Sentinel LNs were negative, excised in 4 patients. The mean tumor size was 5.5 cm and most (82.4%) patients were diagnosed at Stage II disease including some at Stage I and III (7.1%, 10.6%). Docetaxel (Taxotere®) was combined with cyclophosphamide alone or in addition with doxorubicin, epirubicin, 5 FU and trastuzumab either in combination or sequential regimen. Taxotere in combination with adriamycin and cyclophosphamide was planned for 63.5% patients. Trastuzumab as sequential therapy could be afforded by 1 patient only. Data regarding radiotherapy or hormone therapy was not recorded. At the end of four cycles, 83.5% of patients were found disease free and 5.9% had loco regional relapse. At 1 year 71 (93.4%) patients were alive, 63 (88.7%) were relapse-free and 8 (11.2%) had loco regional relapse. Nausea, vomiting, diarrhea, alopecia, anemia and neutropenia were most commonly reported adverse events classified as Grade 1 or Grade 2. Grade 3 neutropenia was reported in 5 patients and 2 patients reported grade 4 neutropenia. Grade 3 diarrhea was reported in 1 patient.&#x0D; Conclusion: Docetaxel as adjuvant chemotherapy offered one year survival in 93.4% (71/76) of the patients and 88.7% (63/71 patients) were disease-free. The safety profile of docetaxel based regimens was expected and manageable.&#x0D; Delta Med Col J. Jan 2019 7(1): 4-10

Anticancer activity of polyphyllin I in nasopharyngeal carcinoma by modulation of lncRNA ROR and P53 signalling

Nasopharyngeal carcinoma (NPC) is the most common aggressive squamous cell carcinoma in head and neck cancers. Although advanced radiochemotherapy has been applied, the prognosis of NPC patients still remains poor due to the regional relapse and distant metastasis. Polyphyllin I (PP I) is extracted from natural herb Paris polyphylla that has been widely used in cancer treatment and long non-coding RNA (lncRNA) has been reported to play a key role in the anti-tumour activity of PP I. In this study, it has been found that PP I inhibited the proliferation and induced apoptosis of NPC cells in a dose-dependent manner. A higher level of lncRNA regulator of reprogramming (ROR) expression was detected in NPC cell lines compared with normal nasopharyngeal cell line and PP I must significantly down-regulate the expression level of lncRNA ROR. LncRNA ROR/P53 signalling was essential for PP I-suppressed NPC progression. These data indicated that PP I suppressed tumour growth and induced apoptosis of NPC in vitro and in vivo through down-regulation of lncRNA-ROR, subsequently upregulating of P53 signalling. LncRNA ROR may be a potential therapeutic target and PP I would be a promising candidate for NPC treatment.

Nodal FDG-PET/CT uptake influences outcome and relapse location among esophageal cancer patients submitted to chemotherapy or radiochemotherapy.

Our aim was investigate whether lymph node uptake is associated with survival and regional relapses, and relapse patterns with respect to the radiotherapy fields in esophageal cancer (EC). The FDG-PET/CT image datasets of 56 patients were analyzed. All patients underwent definitive or neoadjuvant radio/chemotherapy (RCT). All patients suffering from persistent or recurrent local/regional-only disease after RCT were considered for salvage resection. Patients with adenocarcinoma without metastatic disease were considered for planned resection (usually within 3months of treatment). Patients with PET-positive lymph nodes before treatment had a worse overall survival and a shorter disease-free survival than those without PET-positive nodes. They also had worse node and metastatic relapse-free survival. N2 patients had statistically significant poorer outcomes than N1-N0 patients and a better survival if the involved nodes were closer to the esophageal tumor. Involved node location by PET/CT also affected global, nodal and metastatic relapses. In addition, an increment of SUVmax value increased relative risk of death and increased relative risk of node and metastatic relapses. The first site of relapse was metastatic recurrence and, second, local recurrence. The most frequent were "in-field" loco/regional recurrence. We observed a relationship between patients classified-N1 and out-field nodal recurrence (p = 0.024), and between patients-N2 and in-field nodal recurrence. The number of PET-positive nodes was an independent significant prognostic predictor for relapse (p < 0.001). Our study shows that only FDG-PET/CT can provide prognostic information in EC. Nodal PET/CT uptake influences outcome and relapse location among EC patients.

Correlation between changes in the gonial area and postoperative stability in the treatment of mandibular prognathism

IntroductionThe present study was to investigate the relationship between the post-operative area of the gonial region (lateral and frontal) and post-operative relapse. Material and methodsThirty-seven patients, treated for mandibular prognathism were followed with serial lateral cephalograms [pre-operatively (T1), immediately after surgery (T2), and at least 2 years post-operatively (T3)]. The surgical changes (T21), post-operative stability (T32) and 2-year surgical change (T31) were evaluated by the Student's t-test. Pearson's correlation coefficient analysis was used to determine the correlations between the cephalometric parameters. Multiple linear regression analysis was used to assess the association between the risk factors and post-operative relapse. ResultsThe immediate post-operative changes (T21), mean setback of the Me was 12.3 mm and the frontal gonial area (T2) was increased by 138.7 mm2. The final post-operative changes (T31), lateral gonial area was significantly reduced by 190.5 mm2. ConclusionRelapse was significantly correlated with the amount of setback. However, changes in the area of the gonial region (lateral and frontal) showed weak correlation with relapse. Multiple regression analysis also showed poor predictability of relapse. In conclusion, the results of this study showed that significant changes in the area of the gonial region (lateral and frontal) did not affect the maintenance of post-operative stability.

Depth of invasion alone as a prognostic factor in low-risk early-stage oral cavity carcinoma.

To evaluate the significance of increasing depth of invasion (DOI) as the sole risk factor for recurrence in patients with low-risk early-stage oral cavity squamous cell carcinoma (OCSCC). We retrospectively reviewed 560 patients with OCSCC treated at our institution between 2003 and 2013. Patients were included if they had low-risk early-stage OCSCC treated with surgical resection ± neck dissection and no adjuvant therapy. Low risk was defined as absence of positive or close margins, lymphovascular invasion, perineural invasion, and positive lymph nodes. Patients with tumor (T)3-T4 disease were excluded. Pathology specimens were independently re-reviewed by two board-certified pathologists to confirm proper measurement of DOI. Kaplan-Meier and Cox proportional hazards regression analyses were performed to identify factors predictive for recurrence as well as progression-free survival (PFS) and overall survival (OS). A total of 126 patients with low-risk early-stage T1-2N0 OCSCC were included. Median follow-up time was 42.5 months and median DOI was 4 mm. There was no significant difference in incidence of local (P = 0.95), regional (P = 0.81), or distant recurrence (P = 0.96) among patients with DOI < 4 mm versus ≥4 mm. On multivariable analysis, DOI was significant for both PFS (P = 0.03) and OS (P = 0.002). In this study, we show that in the absence of other high-risk pathologic features, DOI ≥ 4 mm does not portend for increased incidence of local, regional, or distant relapse in patients treated with surgery alone; however, increasing DOI is a marker for worse PFS and OS in patients with low-risk, early-stage OCSCC. 4 Laryngoscope, 129:2082-2086, 2019.

Adjuvant interstitial three-dimensional pulse-dose-rate-brachytherapy for lip squamous cell carcinoma after surgical resection.

PurposeThe purpose of this study was to report clinical outcomes of patients treated with pulse-dose-rate brachytherapy (PDR-BT) for lip cancer after insufficient surgery.Material and methodsTwenty lip cancer patients were treated from January 2012 to September 2016. Primary treatment included surgery with or without reconstruction. All patients were diagnosed with squamous cell carcinoma, most of the tumors were pT1. Brachytherapy procedures were done after post-operative wound healing. Median of three plastic tubes were implanted using a free-hand technique. Two PDR-BT treatments were scheduled for every patient, with the gap of median 13 days. The planned dose was 0.8-1 Gy per pulse to the total dose of 50 Gy from two PDR-BT treatments. Patients were evaluated every 3-6 months. Follow-up time was counted from the last day of treatment to any event or last visit. Early and late toxicities were scored with RTOG scale.ResultsAverage follow-up was 34.7 months (range, 12.7-67.6). Three- and five-year estimated disease-free survival was 95% and local control was 100%. One patient suffered from regional relapse in the submental region (IA lymph node group). Skin erythema or dry desquamation (grade 1) or wet desquamation (grade 2) was observed in 13 patients (65%) and one patient (5%), respectively. Six patients presented no acute toxicity. Moreover, there were no complications involving lip mucosa. All patients had grade 1 soft tissue fibrosis in the irradiated area, besides that, late toxicity included only skin complications. There were no significant factors associated with late toxicity ≥ grade 2.ConclusionsPDR-BT in the adjuvant treatment of the lip cancer yields high local control with low toxicity. Even patients with close margins after surgery (< 5 mm) should be considered as candidates for PDR-BT.

High precision radiotherapy including intensity-modulated radiation therapy and pulsed-dose-rate brachytherapy for cervical cancer: a retrospective monoinstitutional study.

PurposeTo analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution.Material and methodsBetween March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) – European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria.ResultsTwo patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy.ConclusionsOur study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Second breast conserving therapy after ipsilateral breast tumor recurrence – a 10-year experience of re-irradiation

PurposeThe aim of this study is to evaluate the efficacy and toxicity of post-operative partial breast re-irradiation with multi-catheter brachytherapy after second breast conserving therapy (BCT) in patients with small, low-risk ipsilateral breast tumor recurrence (IBTR).Material and methodsBetween 2008 and 2018, 19 consecutive patients with low-risk IBTR (max. rpT1 cN0 cM0, Her2 negative, preferably positive hormone receptor status) who refused mastectomy were treated with salvage lumpectomy, followed by post-operative partial breast re-irradiation with multi-catheter brachytherapy. Eight patients were irradiated using PDR brachytherapy (49.8-50.4 Gy in pulses of 0.5-0.7 Gy) and 11 patients using HDR brachytherapy (34.2 Gy in fractions of 3.8 Gy or 32 Gy in fractions of 4 Gy). All patients had undergone prior BCT for their primary tumor, followed by adjuvant whole breast radiotherapy. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS) as well as toxicity were evaluated in the present study.ResultsAfter a median follow-up of 65 months following IBTR (18-120 months), only one second IBTR in 19 patients was diagnosed 77 months after re-irradiation, resulting in a LC rate of 100% at 5 years. DFS and OS rates were both 100% at 5 years following re-irradiation. Except for the above mentioned second IBTR, no regional or distant relapse was recorded. Regarding toxicity, 63% of patients developed adverse events (CTCAE grade ≤ 2), with fibrosis detected in 37% (7/19) of patients, necrosis in 11% (2/19), hyperpigmentation in 47% (9/19), and telangiectasia in 11% (2/19), respectively. No patient showed a high-grade (CTCAE grade ≥ 3) adverse event.ConclusionsIn case of small, low-risk IBTR, adjuvant re-irradiation using multi-catheter brachytherapy is a feasible, safe, and effective treatment method after repeated lumpectomy, and an alternative to mastectomy.

Use of Radiomics Combined With Machine Learning Method in the Recurrence Patterns After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Preliminary Study.

Objective: To analyze the recurrence patterns and reasons in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to investigate the feasibility of radiomics for analysis of radioresistance.Methods: We analyzed 306 NPC patients treated with IMRT from Jul-2009 to Aug-2016, 20 of whom developed with recurrence. For the NPCs with recurrence, CT, MR, or PET/CT images of recurrent disease were registered with the primary planning CT for dosimetry analysis. The recurrences were defined as in-field, marginal or out-of-field, according to dose-volume histogram (DVH) of the recurrence volume. To explore the predictive power of radiomics for NPCs with in-field recurrences (NPC-IFR), 16 NPCs with non-progression disease (NPC-NPD) were used for comparison. For these NPC-IFRs and NPC-NPDs, 1117 radiomic features were quantified from the tumor region using pre-treatment spectral attenuated inversion-recovery T2-weighted (SPAIR T2W) magnetic resonance imaging (MRI). Intraclass correlation coefficients (ICC) and Pearson correlation coefficient (PCC) was calculated to identify influential feature subset. Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were employed to assess the capability of each feature on NPC-IFR prediction. Principal component analysis (PCA) was performed for feature reduction. Artificial neural network (ANN), k-nearest neighbor (KNN), and support vector machine (SVM) models were trained and validated by using stratified 10-fold cross validation.Results: The median follow up was 26.5 (range 8–65) months. 9/20 (45%) occurred in the primary tumor, 8/20 (40%) occurred in regional lymph nodes, and 3/20 (15%) patients developed a primary and regional failure. Dosimetric and target volume analysis of the recurrence indicated that there were 18 in-field, and 1 marginal as well as 1 out-of-field recurrence. With pre-therapeutic SPAIR T2W MRI images available, 11 NPC-IFRs (11 of 18 NPC-IFRs who had available pre-therapeutic MRI) and 16 NPC-NPDs were subsequently employed for radiomic analysis. Results showed that NPC-IFRs vs. NPC-NPDs could be differentiated by 8 features (AUCs: 0.727–0.835). The classification models showed potential in prediction of NPC-IFR with higher accuracies (ANN: 0.812, KNN: 0.775, SVM: 0.732).Conclusion: In-field and high-dose region relapse were the main recurrence patterns which may be due to the radioresistance. After integration in the clinical workflow, radiomic analysis can be served as imaging biomarkers to facilitate early salvage for NPC patients who are at risk of in-field recurrence.