Positive Lymph Research Articles

Identification of Risk Factors Associated with Axillary Lymph Node Metastasis for Sentinel Lymph Node-Positive Breast Cancer Patients

Objective This study aimed to identify clinicopathological factors related to the extent of axillary lymph node (ALN) involvement in early-stage BC patients with positive sentinel lymph nodes (SLNs). Methods This was a retrospective analysis of 566 patients in cT1-2N0M0 with 1-2 positive SLNs that underwent axillary lymph node dissection (ALND) at Sun Yat-Sen Memorial Hospital. The clinical and pathologic data from these patients were analyzed. Results Of these 566 patients, 235 (41.5%) exhibited NSLN metastases. Multivariate analysis revealed that the number of positive SLNs (odds ratio (OR) = 1.511; P=0.038), the ratio of metastatic/dissected SLNs (SLN metastasis rate) (OR = 2.124; P < 0.001), and lymphovascular invasion (LVI) (OR = 1.503; P=0.022) were all independent predictors of NSLN metastasis. Patients with 0, 1, 2, or 3 of these risk factors exhibited NSLN metastases in 29.3%, 35.7%, 50.8%, and 68.3% of cases, respectively. We additionally found that the number of positive SLNs (OR = 3.582; P < 0.001), SLN metastasis rate (OR = 2.505; P=0.001), LVI (OR = 2.010; P=0.004), and HER2 overexpression (OR = 1.774; P=0.034) were all independent predictors of N2 disease. When individuals had 0, 1, 2, 3, or 4 of these risk factors, they had four or more involved ALNs in 5.2%, 10.8%, 21.1%, 37.5%, and 70.6% of cases, respectively. Conclusion These results suggest that the number of positive SLNs, the SLN metastasis rate, and LVI are all significant predictors of ALN status in BC patients that have 1-2 positive SLNs and that have undergone ALND. In addition, HER2 overexpression was a significant predictor of N2 disease.

A negative binomial regression model for risk estimation of 0\u20132 axillary lymph node metastases in breast cancer patients

Extensive clinical trials indicate that patients with negative sentinel lymph node biopsy do not need axillary lymph node dissection (ALND). However, the ACOSOG Z0011 trial indicates that patients with clinically negative axillary lymph nodes (ALNs) and 1–2 positive sentinel lymph nodes having breast conserving surgery with whole breast radiotherapy do not benefit from ALND. The aim of this study is therefore to identify those patients with 0–2 positive nodes who might avoid ALND. A total of 486 patients were eligible for the study with 212 patients in the modeling group and 274 patients in the validation group, respectively. Clinical lymph node status, histologic grade, estrogen receptor status, and human epidermal growth factor receptor 2 status were found to be significantly associated with ALN metastasis. A negative binomial regression (NBR) model was developed to predict the probability of having 0–2 ALN metastases with the area under the curve of 0.881 (95% confidence interval 0.829–0.921, P < 0.001) in the modeling group and 0.758 (95% confidence interval 0.702–0.807, P < 0.001) in the validation group. Decision curve analysis demonstrated that the model was clinically useful. The NBR model demonstrated adequate discriminative ability and clinical utility for predicting 0–2 ALN metastases.

Application of a thyroid cartilage window technique for transoral resection of early glottic cancer involving the anterior commissure

Background Management of early stage glottic carcinoma involving the anterior commissure is challenging. Aims/objectives This study aimed to evaluate the efficacy of a thyroid cartilage window (TCW) technique for transoral laser resection of early glottic cancer with involvement of the anterior commissure. Material and methods Twenty-one patient who underwent a TCW technique for transoral resection early glottic carcinoma involving the anterior commissure, were retrospectively analyzed. The technical nuances, organ preservation rate and voice outcomes, local and regional recurrence, and perioperative comorbidities, were assessed. Results All 21 patients underwent a TCW technique for resection, both the organ preservation rate and negative margin achieved 100%. The local control rate achieved 100%, and the 5 years recurrence free survival was 90.5%. For two patients with subglottic involvement (9.5%), regional recurrence with confirmation of a positive pre-laryngeal lymph node was observed. Postoperative granuloma was detected in all 21 patients, 13 of whom spontaneously disappeared (61.9%); whereas the remaining 8 patients (38.1%) demonstrated a consistent presence of granuloma more than 12 weeks, and they accepted surgical extirpation of granuloma under surface anesthesia. The laryngeal web developed in all 21 patients, while no dyspnea and local recurrence were present. By comparison with preoperative baseline, postoperative self-assessment voice demonstrated a significant improvement (p = .01), while objective voice indices were not significantly altered (p > .05). Conclusions and significance TCW technique is a valuable means for transoral resection of early glottic laryngeal cancer involving the anterior commissure, with acceptable voice quality and seemingly low comorbidities.

What is the Cost-Effective Treatment for Melanoma Patients with a Positive Sentinel Node?

Survival for positive sentinel lymph node (SLN) patients does not differ between completion lymph node dissection (CLND) and nodal observation (OBS). However, treating these patients with CLND and checkpoint inhibitors, such as pembrolizumab (PEM), improves outcomes. This study evaluated the cost-effectiveness of OBS, CLND, and CLND with PEM (CLND-PEM) treatments. A Markov model was designed to simulate treatment for a theoretical cohort of 1000 positive SLN patients per therapy with a 5-year follow-up period. An intervention was cost-effective if its incremental cost-effectiveness ratio among therapies was below the willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Compared with CLND or CLND-PEM, OBS resulted in fewer lymphedema cases but in more disease recurrences. Compared with OBS, CLND had higher costs and lower QALYs. Although CLND-PEM had a lower number of recurrences and deaths than OBS or CLND, it had higher costs and lower QALYs than OBS, and thus was not cost-effective. However, with the effects of CLND from CLND-PEM removed, allowing evaluation of PEM effects alone (PEM alone), the resulting QALYs were the highest, but PEM alone still was not cost-effective compared with OBS ($1.2 million per QALY). By reducing the drug cost to less than $14,404 per patient, PEM alone would become cost-effective. Compared with CLND, CLND-PEM, and PEM alone, OBS was cost-effective for managing positive SLN patients. Although CLND-PEM and PEM alone result in fewer recurrences and deaths, these therapies were not cost-effective due to the quality-of-life decrement of CLND and the current high drug cost of PEM.

Assessment of Post-Resuscitation Intestinal Injury and Timing of Bacterial Translocation in Swine Anaesthetized With Propofol-Based Total Intravenous Anaesthesia.

Introduction and objectivesBacterial translocation (BT) is the passage of viable bacteria or endotoxins from the gastrointestinal lumen to extra-luminal tissues and is usually observed after intestinal ischaemia-reperfusion injury. The aim of this study was to investigate post-resuscitation BT after cardiac arrest and resuscitation in a swine anaesthetized with propofol-based total intravenous anaesthesia.Materials and methodsEighteen female Landrace/Large White piglets were randomly divided into control (CON), cardiac arrest (CA) and cardiac arrest-cardiopulmonary resuscitation (CA-CPR) groups. In the CON group, the animals were only monitored for two hours. In the CA group, the animals were not resuscitated and underwent necropsy immediately after cardiac arrest. In the CA-CPR group, the animals were resuscitated until the return of spontaneous circulation (ROSC) and were monitored for two hours. The animals of the CON and CA-CPR groups underwent necropsy 24 hours later. Bacterial translocation was assessed by blood and tissue cultures and endotoxin measurement in the portal and systemic circulation. Malondialdehyde content calculation and histological analysis of the intestine were performed in order to estimate ischemia and reperfusion (I/R) tissue damage.Results Malondialdehyde content, an indicator of oxidative stress, was significantly higher in the CA-CPR group compared to the CA in homogenized ileum (p=0.016). Malondialdehyde content in homogenized colon revealed significantly higher levels in the CA-CPR group compared to the CON (p=0.004) and the CA group (p=0.016). We found significantly higher levels of portal endotoxin in the CA-CPR group compared to the CON (p=0.026) and the CA group (p=0.026). The number of positive mesenteric lymph nodes cultures for E. coli was greater in the CA-CPR group, followed by the CA and CON groups, although the difference was not significant (67%, 33%, and 33%, respectively; p=0.407).ConclusionsMalondialdehyde content and portal endotoxin levels do not increase during the cardiac arrest interval, but only after CPR and ROSC. Although the number of positive MLNs cultures was greater in the CA-CPR animals, no statistically significant differences were observed between the three groups due to the short monitoring period.

Occurrence of metastatic eccrine porocarcinoma in an immunosuppressed patient

BackgroundEccrine porocarcinoma is a rare malignancy accounting for 0.005 to 0.01% of all cutaneous tumors. However, its etiology is not well established. Herein we are reporting the occurrence of metastatic porocarcinoma of the back in a patient with a history of multiple cutaneous malignancies and chronic immunosuppression.Case presentationA 79-year-old male with a history of long-term immunosuppressive therapy for left lung transplantation and multiple cutaneous malignancies including melanoma, presented with an enlargening plaque on the right upper back. Biopsy demonstrated an infiltrative epithelial tumor with aggressive histology and ductal formation. Immunohistochemical stains for p63, CK-5/6, and CEA were diffusely positive, while CK-7 and CK-20 were negative. A diagnosis of eccrine porocarcinoma was made. He underwent complete wide excision with negative margins of the right upper back in January 2018. In November 2018, he was found to have a right posterior shoulder mass, positive right axillary lymph nodes, superficial right upper back soft tissue masses and lymphangitic carcinomatosis involving the left lung. He was transitioned to comfort care and subsequently passed from metastatic disease in December 2018.ConclusionThe occurrence of eccrine porocarcinoma in a patient on long term immunosuppressive therapy for lung transplantation suggests a possible role for chronic immunosuppression in the induction of a subset of eccrine porocarcinomas, as in other cutaneous malignancies.

Analyzing non-sentinel axillary metastases in patients with T3\u2013T4 cN0 early breast cancer and tumor-involved sentinel lymph nodes undergoing breast-conserving therapy or mastectomy

PurposeIn the ACOSOG Z0011 trial, completing axillary lymph node dissection (cALND) did not benefit patients with T1–T2 cN0 early breast cancer and 1–2 positive sentinel lymph nodes (SLN) undergoing breast-conserving surgery (BCT). This paper reports cALND rates in the clinical routine for patients who had higher (T3–T4) tumor stages and/or underwent mastectomy but otherwise met the ACOSOG Z0011 eligibility criteria. Aim of this study is to determine cALND time trends and non-sentinel axillary metastases (NSAM) rates to estimate occult axillary tumor burden.MethodsData were included from patients treated in 179 German breast cancer centers between 2008 and 2015. Time-trend rates were analyzed for cALND of patients with T3–T4 tumors separated for BCT and mastectomy and regarding presence of axillary macrometastases or micrometastases.ResultsData were available for 188,909 patients, of whom 19,009 were identified with 1–2 positive SLN. Those 19,009 patients were separated into 4 cohorts: (1) Patients with T1–T2 tumors receiving BCT (ACOSOG Z0011 eligible; n = 13,741), (2) T1–T2 with mastectomy (n = 4093), (3) T3–T4 with BCT (n = 269), (4) T3–T4 with mastectomy (n = 906). Among patients with T3–T4 tumors, cALND rates declined from 2008 to 2015: from 88.2 to 62.6% for patients receiving mastectomy and from 96.6 to 58.1% in patients receiving BCT. Overall rates for any NSAM after cALND for cohorts 1–4 were 33.4%, 42.3%, 46.9%, 58.8%, respectively.ConclusionsThe cALND rates have decreased substantially in routine care in patients with ‘extended’ ACOSOG Z0011 eligibility criteria. Axillary tumor burden is higher in these patients than in the ACOSOG Z0011 trial.

Rational surgical neck management in total laryngectomy for advanced stage laryngeal squamous cell carcinomas

PurposeControversies exist in regard to surgical neck management in total laryngectomies (TL). International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY).MethodsThirty-seven consecutive primary TL cases from 2009 to 2019 were retrospectively analyzed in terms of local tumor growth using a previously established imaging scheme, metastatic neck involvement, and NY impact on survival.ResultsThere was no case of level IIB involvement on any side. For type A and B tumor midline involvement, no positive contralateral lymph nodes were found. Craniocaudal tumor extension correlated with contralateral neck involvement (OR: 1.098, p = 0.0493) and showed increased involvement when extending 33 mm (p = 0.0134). Using a bilateral NY of ≥ 24 for 5-year overall survival (OS) and ≥ 26 for 5-year disease-free survival (DFS) gave significantly increased rate advantages of 64 and 56%, respectively (both p < 0.0001).ConclusionsThis work sheds light on regional metastatic distribution pattern and its influence on TL cases. An NY of n ≥ 26 can be considered a desirable benchmark for bilateral selective neck dissections as it leads to improved OS and DFS. Therefore, an omission of distinct neck levels cannot be promoted at this time.

Laparoscopic Sentinel Node Mapping with Surgical Staging following Hysteroscopic Endometrial Resection in Endometrial Stromal Sarcoma

A 50-year-old woman presented with symptoms of abnormal uterine bleeding. Ultrasonography showed an intrauterine cavity nodule sized approximately 2 cm. A hysteroscopic resection was diagnosed. The histopathology revealed high-grade endometrial stromal sarcoma. The surgery was laparoscopic surgical staging with indocyanine green sentinel lymph node mapping. Two positive indocyanine green sentinel lymph node of the right and left pelvic nodes showed no nodal metastasis. Also, the five positive indocyanine green sentinel lymph node showed no nodal metastasis. The occult lymph nodes were dissected at the right and left pelvic nodes for nodes 4 and 9, respectively. Conclusively, hysteroscopic resection is beneficial for the diagnosis of uterine sarcoma. Notwithstanding, laparoscopy can be used for uterine cancer and the indocyanine green sentinel lymph node showed no false negative. The patient was stage IA.

Independent risk factors for axillary lymph node metastasis in breast cancer patients with one or two positive sentinel lymph nodes

BackgroundThe benefit of axillary lymph node dissection (ALND) in breast cancer patients with one or two positive sentinel lymph nodes (SLNs) remains inconclusive. The purpose of this study was to identify risk factors independently associated with axillary lymph node (ALN) metastasis.MethodsWe retrospectively analyzed data from 389 Chinese breast cancer patients with one or two positive SLNs who underwent ALND. Univariate and multivariate logistic regression analyses were performed to identify ALN metastasis-associated risk factors.ResultsAmong the 389 patients, 174 (44.7%) had ALN metastasis, while 215 (55.3%) showed no evidence of ALN metastasis. Univariate analysis revealed significant differences in age (< 60 or ≥ 60 years), human epidermal growth factor receptor-2 (Her-2) status, and the ratio of positive to total SLNs between the ALN metastasis and non-metastasis groups (P < 0.05). The multivariate analysis indicated that age, the ratio of positive to total SLNs, and occupations were significantly different between the two groups. Lastly, younger age (< 60 years), a higher ratio of positive to total SLNs, and manual labor jobs were independently associated with ALN metastasis (P < 0.05).ConclusionsThe risk of ALN metastasis in breast cancer patients with one or two positive SLNs can be further increased by younger age, manual labor jobs, and a high ratio of positive to total SLNs. Our findings may also aid in identifying which patients with one or two positive SLNs may not require ALND.

CT-guided Reflector Localization of a Previously Positive Axillary Lymph Node after Neoadjuvant Chemotherapy in a Breast Cancer Patient

CT-guided Reflector Localization of a Previously Positive Axillary Lymph Node after Neoadjuvant Chemotherapy in a Breast Cancer Patient

Can neoadjuvant chemotherapy improve survival in stage T3-4N1 nasopharyngeal carcinoma? A propensity matched analysis

BackgroundTo estimate the efficacy of neoadjuvant chemotherapy (NCT) in stage T3-4N1 nasopharyngeal carcinoma (NPC).MethodsData on stage T3-4N1 NPC patients treated with concurrent chemoradiotherapy (CCRT) with or without NCT at the Sun Yat-sen University Cancer Center between January 2006 and December 2013 were retrospectively reviewed. Propensity score matching (PSM) was carried out to balance prognostic factors in NCT followed by CCRT (NCT + CCRT) group and CCRT group in a 1:1 ratio. Survival outcomes of matched patients in the two groups were compared, and prognostic factors were identified using Cox regression model.ResultsA total of 282 patients were involved in this study, with 136 of NCT + CCRT group and 146 of CCRT group. After PSM, 85 pairs of patients were selected. There were no significant differences in 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and recurrence-free survival (RFS) between NCT + CCRT group and CCRT group (81.0% vs. 77.5%, P = 0.750; 85.8% vs. 88.1%, P = 0.495; 92.5% vs. 93.9%, P = 0.759; 81.0% vs.77.5%, P = 0.919, respectively). Multivariate analysis found that smoking history (P = 0.044) and T classification (P = 0.027) were independent prognostic factors for OS, lymph node diameter (P = 0.032) was independent prognostic factor for LRFS, positive pretreatment lymph node condition (PLNC), which was defined as the lymph node necrosis or confluent, was independent prognostic factor for DRFS (P = 0.007), and RFS (P = 0.009). Lower 5-year OS (82.7% vs. 94.1%, P = 0.014), DRFS (79.3% vs. 96.2%, P = 0.003), and RFS (62.4% vs. 86.8%, P = 0.001) were found in positive PLNC group compared with negative PLNC group. In terms of toxicities, the incidences of acute hematological Grade 3–4 adverse events (AEs) were higher in NCT + CCRT group compared with CCRT group (P < 0.05), while no significant difference was observed in the rates of non-hematological Grade 3–4 AEs between these two groups (P > 0.05).ConclusionsAdditional NCT is not associated with improved survival outcomes for patients with stage T3-4N1 NPC, but bring increased hematological Grade 3–4 AEs. PLNC is independent prognostic factor in stage T3-4N1 NPC, with positive PLNC correlating with poor survival outcomes.

Effect of hypofractionation on the incidental axilla dose during tangential field radiotherapy in breast cancer

ObjectiveTangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed.Materials and methodsBiological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/β ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases.ResultsThe extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient’s anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules.ConclusionOur data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

Adjuvant systemic therapies for melanoma in Alberta: An early descriptive analysis of population characteristics and treatment outcomes.

e22013 Background: Adjuvant immunotherapies and adjuvant targeted therapy for melanoma became available in clinical practice in 2018 in Alberta, Canada. We describe the delivery of adjuvant systemic therapy, local-regional treatment, recurrence patterns, and treatment toxicity, in tertiary academic centers. Methods: We conducted a retrospective chart review of patients who received adjuvant systemic therapy for melanoma in Alberta. Adjuvant systemic treatment options included Nivolumab, Pembrolizumab, and Dabrafenib/Trametinib. Results: From September 2017 to January 2020, 71 patients were identified. Forty-one (61%) were male with a median age of 60 years (15-88). Seven (9.8%), 26 (36.6%), 27 (38%), 4 (5.6%), and 3 (4.2%) patients were stage IIIA, IIIB, IIIC, III-unspecified, and IV, respectively. BRAF mutations were detected in 31 (50.8%) patients. The median time from last surgical procedure to start of treatment was 10.8 weeks (4-28), with a median follow up time of 12 months. Sixty-one patients (85.9%) received Nivolumab, four (5.6%) patients received Pembrolizumab, and four (5.6%) Dabrafenib/Tremetinib. Twenty-eight (87.5%) of 32 patients with a positive sentinel lymph node biopsy did not complete elective regional lymph node dissection. Only two patients received adjuvant radiation. Local-regional surveillance with regular nodal ultrasound was not consistently performed. Seven (9.8%) patients had clinical or radiographic finding of enlarged regional lymph node while on treatment. At time of analysis, thirteen (18.3%) patients have completed adjuvant therapy, 18 (25.3%) discontinued therapy, and 39 (54.9%) patients were still on treatment. Eleven (15.4%) patients discontinued treatment due to toxicity, 8 (13.1%) from Nivolumab, 3 (75%) from Dabrafenib/Trametinib. Nine (12.6%) patients relapsed on treatment, of those, five (55.5%) had incidental findings on baseline imaging. Hypothyroidism affected 11 (15.4%) patients, hypophysitis and other immune-related side effects were described in 14 (19.7%) cases. Conclusions: Our cohort reflects excellent patient selection and delivery of adjuvant therapy consistent with clinical trial data. Surgical and radiation oncology care has adapted, and differs from trial procedure. Adjuvant immunotherapy was used in most patients. There appears to be a higher rate of discontinuation due to toxicity with Dabrafenib/Trametinib. Toxicity and recurrence findings are preliminary and will be updated.

Validation of nomograms to predict non-sentinel lymph node metastasis after positive sentinel lymph node in breast cancer: Indian cohort background.

568 Background: Axillary lymph node metastasis is still the important prognostic factor in the management of breast cancer (BC). Where we have moved towards axillary conservation in clinically node negative (cN0), the debate on what after 1-2 sentinel lymph nodes positive (SLN+ve) still continues. The ideal situation would be wherein we can accurately predict which patient has a risk of additional non SLN+ve. Several nomograms have been developed to predict the risk of NonSLN+ve. But in view of the differences in tumor size and nodal burden between our patients and the western data, we conducted a study to validate some of these nomograms in our cohort of early BC with positive LN on Low axillary sampling (LAS). Methods: Clinico-pathological data was collected for operable BC (OBC) with cN0 who underwent upfront SLNB or AS. This was entered into the various nomograms and the probability of the Non SLN+ve was calculated. Nomograms with AUC of greater than 0.7 were pre-defined as considerable discrimination. Results: From 2013 to 2018, 2350 women with cN0 OBC underwent LAS. Of which, 670 (28.5%) had a positive node on LAS. Median pT size was 3 cm with 327 (48%), LVI +ve 152 (77%) ENI +ve, 525 (78.4%) Hormone receptor +ve and 485 (72.4%) grade 3 tumors. Of 670, 239 (35.7%) had a NonSLN+ve on completion axillary dissection. The AUC values for nomograms included,ie. MSKCC, MDAnderson, Tenon, Cambridge, Shanghai, Mayo clinic and Turkish were 0.769, 0.77, 0.55, 0.74, 0.65, 0.529, 0.563 respectively. Only three nomograms, MDA, MSKCC and Cambridge had an AUC of more than 0.7. However, they were associated with poor sensitivity and specificity and high FNR (Table) making them clinically unreliable for this cohort. Conclusions: All 7 nomograms were not validated in our study. The larger T size and higher nodal burden of our cohort may be responsible for the same. We thus need to develop an Indian nomogram to predict the risk of non SLN+ve for our patients. [Table: see text]

Gastric-type adenocarcinoma of the cervix: Genomic drivers and clinical outcomes.

6030 Background: Cervical Gastric-type adenocarcinoma (CGA) is a non-HPV-associated adenocarcinoma, comprising 10% of all cervical adenocarcinomas (Park et al, 2019). The optimal management approach is unclear, given that most data in advanced cervical cancer is driven by HPV-positive disease. We summarize our experience with this rare tumor type at a large cancer center. Methods: A retrospective review was performed for all women diagnosed with CGA 6/1/2002- 7/1/2019. Patients who did not follow up after a single visit were excluded. Kaplan-Meier survival analysis was performed to determine progression-free survival (PFS) and overall survival (OS) from date of diagnosis. Tumors from a subset of patients were subjected to MSK-IMPACT targeted sequencing and analysis (Zehir et al, 2017). Results: A total of 68 women were identified; 47 met inclusion criteria. The median age at diagnosis was 52 years (range 27-83). The majority of patients were white (70%), an additional 19% were Asian. The majority of patients (60%, n=28) presented with advanced disease (FIGO 2018, stage II-IV), while 40% (n=19) were Stage I. Of note, 26% (n=12) had positive pelvic lymph nodes and 13% (n=6) had ovarian metastases at time of surgical resection. For upfront treatment: 13% (n=6) had surgery alone of whom 83% had stage 1 disease, 36% (n=17) had surgery followed by adjuvant therapy, 30% (n =14) received definitive chemo-radiation (CRT). All patients with stage IV disease 15% (n=7) received chemotherapy alone. At completion of primary treatment, 19% (n=9) of patients had persistent disease. In patients who received CCRT, 65% (n=22) recurred, the majority (64%) within 12 months of completion of upfront therapy. Pelvic recurrence was the most common site (n=14, 64%). With a median follow up time of 30 months (range 1-159), the median PFS for Stage I was 34.4 months, compared to 17.5 months in patients with Stage II-IV disease (p= 0.29). Of the 24 patients that had MSK-IMPACT, the most common mutation was TP53 (n=16, 64%) followed by mutations in the RAS pathway (n=8, 33%), PIK3CA (n=3, 12.5%), STK11 (n=3, 12.5%), and ERBB2 alterations (n=2, 8.3 %). 2 (8.3%) women enrolled on a clinical trial based on their NGS results, one targeting ERBB2 and one targeting PIK3CA. Conclusions: Consistent with prior published literature, CGA is an aggressive form of cervical cancer with poor median OS in the advanced setting. With universal HPV vaccination, HPV negative cervical cancer will represent a larger percentage of newly diagnosed cancers and further research is needed to identify the optimal management approach.

A phase Ib trial of neoadjuvant/adjuvant durvalumab +/- tremelimumab in locally advanced renal cell carcinoma (RCC).

5021 Background: Effective neoadjuvant and adjuvant therapies are lacking in locally advanced RCC. Given robust activity of checkpoint inhibitors in mRCC, a phase Ib trial of perioperative Durvalumab (D) +/- Tremelimumab (T) in locally advanced RCC was conducted (NCT02762006). Methods: Pts with radiographic evidence of high risk localized RCC (clinical stage T2b-4 and/or N1, M0 disease), adequate performance status, and adequate laboratory values were eligible. Primary objective was safety and feasibility of neoadjuvant/adjuvant D +/- T. Results: Twenty-nine pts were enrolled. Cohorts, regimens, and immune-related adverse events (irAE) are detailed in the table. In total, 79% male, median age 61 (range, 42-84), 8%/88%/4% clinical T2/T3/T4, 27% positive clinical lymph nodes (LN+), and median time from neoadjuvant dose to surgery was 7 days. On surgical pathology: 5%/14%/77%/5% pathologic T1/T2/T3/T4, and 13% LN+. Median time from treatment to first grade (Gr) &gt;3 irAE or any Gr irAE requiring corticosteroids was 99 days (range, 32-207). There were no treatment-related delays to nephrectomy or surgical complications. Although not meeting the protocol-defined MTD, given higher than expected irAEs, the study was suspended. Conclusions: Perioperative durvalumab in locally advanced RCC appears safe. The addition of tremelimumab is associated with higher rates of toxicity. Updated toxicity will be presented. Clinical trial information: NCT02762006 . [Table: see text]

ASO Author Reflections: Adjuvant Therapy is Effective for Melanoma Patients with Positive Sentinel Lymph Node Biopsy Who Forgo Completion Lymphadenectomy.

ASO Author Reflections: Adjuvant Therapy is Effective for Melanoma Patients with Positive Sentinel Lymph Node Biopsy Who Forgo Completion Lymphadenectomy.

Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis

BackgroundDue to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients.MethodsIn this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS).ResultsBetween May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27–96 years). The median follow-up was 39 months (range 3–89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14–0.74).ConclusionsTamoxifen treatment was associated with improved DFS for MBC patients.Clinical trial registrationDRKS00009536.

Significance of a positive sentinel lymph node biopsy in staging for distant metastasis in breast cancer: are current guidelines relevant?

In breast cancer, early identification of distant metastasis changes management. Current guidelines recommend radiological staging in patients with a preoperative positive axilla; no guidelines address a preoperative negative axilla with subsequent positive sentinel lymph node biopsy. This study investigates whether current guidelines adequately identify distant metastasis in a positive sentinel lymph node biopsy population that had radiological staging. Patients diagnosed with primary breast cancer between 1 January 2013 and 1 October 2017 with a positive sentinel lymph node biopsy and subsequent radiological staging from a single unit were included. A systematic search identified relevant guideline criteria, against which patients were audited. A total of 330 patients with positive sentinel lymph node biopsy were identified; 227 (69%) had radiological staging postoperatively with computed tomography (5.3%), bone scan (2.6%) and both (92%) which identified 8/227 (3.5%) patients had distant metastasis. Patients with distant metastasis (DMp) compared with those without distant metastasis (NDMp) were associated with poorly differentiated tumours (DMp 62% vs NDMp 28%; p = 0.037), high-grade ductal carcinoma in situ (DMp 75% vs NDMp 39%; p = 0.043) and increased mean invasive tumour size (DMp 37mm vs NDMp 24mm; p = 0.014). Binomial logistic regression did not identify any characteristics to predict distant metastasis in staged patients (chi-squared p = 0.162). Two guidelines used postoperative results to inform radiological staging decision; 68/227 (30%) of staged patients met these guideline criteria, five of eight patients with distant metastasis did not meet current guideline criteria for radiological staging. Over 50% of patients with distant metastasis did not meet current guideline criteria for radiological staging and would have remained undiagnosed if current guidelines were followed. This study had an acceptable detection rate of 3.5% for distant metastasis. We therefore recommend radiological staging in all patients with positive sentinel lymph node biopsy.