N2-N3 Disease Research Articles

The role of radical cystectomy and lymphadenectomy in the management of bladder cancer with clinically positive lymph node involvement.

The role of radical cystectomy and pelvic lymph node dissection in muscle-invasive bladder cancer (MIBC) with clinically positive lymph nodes is debated. This review examines the role of surgery in treating patients with clinical N1 and more advanced nodal involvement (N2-N3) within a multimodal treatment approach. For clinical N1 disease, guidelines typically recommend neoadjuvant chemotherapy followed by surgery. However, for N2-N3 disease, guidelines vary. Advances in diagnostics, systemic therapies, and surgical recovery have improved the prognosis for these patients. Research is increasingly identifying MIBC patients, including those with positive nodes, who may achieve complete pathologic response and long-term survival, supporting the role of surgery even in advanced nodal stages. Managing MIBC with clinically positive lymph nodes, especially in N2-N3 disease, requires a tailored approach. While neoadjuvant chemotherapy followed by radical cystectomy is standard for N1 disease, the role of surgery in advanced nodal stages is growing because of better patient selection and treatment strategies. Emerging evidence suggests that consolidative surgery may improve outcomes in these complex cases.

Short-term and long-term survival outcomes in patients with invasive lobular carcinoma vs. invasive ductal carcinoma of the breast.

e12564 Background: Invasive lobular carcinoma (ILC) accounts for 10% of all invasive breast cancer and has distinct histological and biological features compared to the most common breast cancer histological subtype, invasive ductal carcinoma (IDC). ILC is more endocrine sensitive and chemotherapy resistant than IDC and has a different metastatic pattern. There is lack of conclusive data on the differences in survival outcomes between ILC and IDC. We aimed to assess the short-term and long-term survival outcomes in patients with ILC and IDC in a large population database. Methods: This is a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results database. We included women > 18 years with stage I-III ILC or IDC diagnosed from 1992-2020. Multivariable logistic regression was used to assess factors associated with different treatment modalities in patients with IDC vs. ILC. We estimated breast cancer-specific survival (BCSS) using Kaplan-Meier methods and their survival rates were compared using the log-rank test. We analyzed BCSS at different time points using a cox regression model with time-varying coefficients. Results: 343,397 patients with IDC and 39,859 patients with ILC were included in this study. Patients with ILC were older (63.0 ± 12.5 years vs. 59.2 ± 13.5 years, p<0.001). There were more non-Hispanic white patients with ILC vs. IDC (76% vs. 67%, p<0.001). Patients with ILC had more advanced disease: more stage III disease (16% vs. 11%, p<0.001), more T3-T4 disease (15% vs. 6%, p<0.001), and more N2-N3 disease (12% vs. 9%, p<0.001). Patients with ILC also had a higher frequency of hormone receptor positive disease (97% vs. 81%, p<0.001). Fewer patients with ILC had grade 3-4 tumors (9% vs. 36%, p<0.001). Our multivariate analysis showed that compared to patients with IDC, patients with ILC were more likely to undergo mastectomy (OR=1.85, p < 0.001) and radiation (OR=1.20, p<0.001), but less likely to receive chemotherapy (OR= 0.92, p<0.001). After adjusting for clinicopathological features, treatment modalities, and socioeconomic variables; compared to patients with IDC, patients with ILC had better BCSS in the first five years (HR=0.71, p <0.001), but worse BCSS in later years (HR=1.30, p<0.001 in year 6-10; HR=1.75, p<0.001 in year 11-15; HR=2.17, p<0.001 in year 16-20). Annual hazard models show that IDC peaked at recurrence in the first 5 years after diagnoses, and the hazard rate declines gradually after that. ILC peaked at recurrence in the first 5 years after diagnosis with minimal decrease in hazard rates after that. Conclusions: BCSS of patients with ILC is better in early years but worse in later years compared to patients with IDC. Future studies are needed to identify predictors of late relapses in ILC, and novel therapeutic strategies are required for these patients.

Disparities in patients with HER2-positive breast cancer receiving optimal treatment: Analysis of the real-world ASCO CancerLinQ dataset.

e13739 Background: Racial/ethnic disparities in locoregional second breast cancer events (SBCE) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) are not well defined. We examined rates of SBCE and overall survival (OS) by race and ethnicity in the ASCO CancerLinQ Discovery (CLQD) real-world dataset in HER+ BC pts receiving optimal and not-optimal treatment. Methods: CLQD was used to identify pts undergoing surgery for stage I-III HER2+ BC from 2005-2022. Race/ethnicity were self-reported. Optimal treatment was defined as HER2-directed therapy for stage II-III HER2+ BC starting in 2008, adjuvant endocrine therapy for hormone-receptor positive (HR+) HER2+ BC, radiation after lumpectomy, and regional nodal irradiation for N2-N3 disease. The primary endpoint was SBCE defined as a second event in the ipsilateral or contralateral breast or axilla, with OS as a secondary endpoint. Kaplan-Meier analysis was used to estimate SBCE-free survival and OS. Results: Of 8,795 stage I-III HER2+ BC pts, 5,487 (62.4%) were Non-Hispanic White (NHW), 1,083 (12.3%) Non-Hispanic Black (NHB), 418 (4.7%) Hispanic, 323 (3.7%) Asian or Pacific Islander (API), and 1,484 (16.9%) other/unknown. Overall, 39.2% had HR-HER2+ and 60.7% had HR+HER2- BC. NHW pts were the most likely to present with stage I disease (40.2% vs 31.9%, 29.0%, and 30.3% of NHB, Hispanic, and API pts, respectively, p<0.01) and less likely to be age <50 at diagnosis (26.1% vs 32.3%, 41.0%, and 36.6% in NHB, Hispanic, and API, p<0.01). Overall, 54.2% of HER2+ BC pts received optimal treatment: 54.1%, 60.2%, 60.5%, and 58.8% of NHW, NHB, Hispanic, and API pts (p<0.01). Neoadjuvant HER2-therapy was given in 42.4%, 46.3%, 53.8%, and 51.2% of NHW, NHB, Hispanic, and API pts (p<0.01) and endocrine therapy in 64.7%, 56.8%, 59.3%, and 54.7%, respectively (p<0.01). 5-yr SBCE-free survival and OS are shown (Table). SBCE-free survival was not statistically different by race and ethnicity in optimally or non-optimally treated pts. Optimal treatment increased OS by 4.1% and 0.9% in NHW and NHB pts with HR-HER2+ BC and 2.4% and 8.9% in NHW and NHB pts with HR+HER2+ BC. Conclusions: Differences in OS, but not SBCE, were seen by race/ethnicity in HER2+ BC. OS differences were not completely mitigated by receipt of optimal treatment. [Table: see text]

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial

Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Optimal Size Threshold for MRI-Detected Retropharyngeal Lymph Nodes to Predict Outcomes in Nasopharyngeal Carcinoma: A Two-Center Study.

BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.

Is it the Type of Axillary Surgery or the Number of Removed Lymph Nodes That Increases the Risk of Breast Cancer Related Lymphedema (BCRL)? Results from a Prospective Screening Trial

Axillary surgery has been identified as the main risk factor for BCRL regardless the delivery of regional nodal radiation (RLNR). Yet it remains unknown if it is the type of axillary surgery or the number of removed lymph nodes (LN) that increases BCRL risks. Between 2008 and 2021, 3,350 patients (pts) who received surgery for breast cancer were enrolled in a lymphedema screening trial. Patients with bilateral breast cancer or without axillary surgery were excluded. Perometry was used to assess limb volume preoperatively in all patients. BCRL was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. The cohort was divided by axillary surgery type: axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). Radiation was delivered using 3D conformal technique and RLNR was defined as the usage of anterior supraclavicular field. No hypofractionation was used and doses ranged between 50 and 50.4 Gy in 25-28 fractions. Multivariable Cox proportional hazard models compared the cumulative incidence of BCRL and local failure between different patient groups. After applying inclusion criteria, 2,623 pts were available with overall median follow-up s of 6.1 years. Of the entire cohort, 709 (27%) had ALND with a median of 16 LN removed, while 1,914 (73%) received SLNB only with a median of 2 LN removed. The median number of malignant LN and patients receiving RLNR was higher in ALND group compared to SLNB only group. Frequency distribution analysis showed that the main overlap between ALND and SLNB only groups happen in the range of 3-11 LN removed. Therefore, the primary analysis focused only on pts with 3-11 LN across both groups (n = 690: ALND n = 140, SLNB n = 550). The multivariable model adjusted for BMI, RLNR, age and breast surgery showed that in this group with 3-11 LN removed in both cohorts, ALND remained significantly associated with BCRL (HR: 4.2, p<0.0001). Separate analyses for the entire SLNB only group and ALND groups were conducted to evaluate if the BCRL risk increases per each removed LN within the same axillary surgery group. The multivariable analysis for SLNB only pts(N = 1,914) showed that for each LN removed the risk of BCRL did not increase significantly (HR:1.06, p = 0.3), similarly for ALND group (N = 709) for each LN removed (HR:1.02, p = 0.08). For pts with pathologic N2-N3 disease and clinical node negative without neoadjuvant chemotherapy receiving ALND, the number of LN removed did not significantly improve neither Local control (HR:1.02, p = 0.8) nor distant disease survival (HR:1.01, p = 0.6). ALND procedure per se is the main risk factor for BCRL not the number of LNs removed. For high-risk pts with >N2 disease, aggressive ALND did not improve tumor outcome. De-escalation with targeted axillary sampling followed by RLNR should be evaluated. Future lymphedema research should account for type of axillary surgery instead of number of LNs removed as a factor. (NCT01521741).

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. A total of 178 patients were included in the study. The median follow-up period was 26months (range 3-56months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Association of ipsilateral radiation therapy with contralateral lymph node failure in patients with squamous cell carcinoma of the oral cavity: A systematic review and meta-analysis.

Ipsilateral neck radiotherapy (INRT) is controversial in some patients with oral cavity cancer due to concern for contralateral neck failure (CNF). A systematic review was performed and data were extracted following PRISMA guidelines. Outcomes were the rate of CNF following INRT and the rates of CNF by AJCC 7th ed. tumor and nodal staging. Fifteen studies consisting of 1825 patients were identified. Among the 805 patients treated with INRT, the rate of CNF was 5.7%. Patients with T4 tumors constituted 56% of all CNF cases. The rate of CNF increased by N stage (N0: 1.2%; N1: 3.8%; N2-N3: 17.4%) and was significantly higher for patients with N2-N3 than N0-N1 disease (p < 0.001). INRT is associated with an overall low risk of CNF in well-selected patients with N0-N1 disease. Patients with N2-3 and/or T4 disease should receive bilateral RT due to increased risk of CNF following INRT.

Lack of hierarchical survival prognosis in AJCC staging for colon cancer: Implications for future summary stage classification.

256 Background: Current staging for colon cancer utilizing the American Joint Committee on Cancer TNM framework stratifies disease into groups according to how advanced the disease is and provides important standardized, individual prognostic information. Ideally, staging systems should exhibit hierarchical logic, with increasing stage reflecting worse prognosis. We sought to evaluate hierarchy within the 8th edition AJCC staging system for colon cancer. Methods: All patients with primary colon (including rectosigmoid) cancer diagnosed 2010-2017 were identified from the National Cancer Database (NCDB). Patients were only included if they carried a histologic diagnosis of invasive primary (non-recurrent) cancer, underwent radical surgery, and had complete pathologic staging data (T, N, M category data). Patients with missing follow-up data were excluded. Kaplan-Meier curves were used to assess overall survival by AJCC 8th edition pathologic summary stage group to determine whether staging was hierarchical for colon cancer. Multivariable modeling and log likelihood ratio test was then used to identify relative contributions of T and N variables to overall survival. Results: Among 270,584 colon cancer patients, pathologic staging was noted to be hierarchical by T category alone and by N category alone. However, summary staging was non-hierarchical in both instances. Multivariable modeling confirmed the AJCC non-hierarchy issue (colon HRs: 1, 1.54, 2.62, 2.60, 1.02, 2.15, and 4.38 for stage 1 as reference, 2a, 2b, 2c, 3a, 3b, 3c respectively). Multivariable modeling demonstrated that high T category (T4a, T4b) conferred the greatest risk of mortality based on hazard ratio (T4a HR 2.76, T4b HR 3.04), while high T category as well as high N category (N2a, N2b) contributed substantially to the survival model based on z-score. Further modeling assessing the predictive power of T and N category with respect to overall survival demonstrated that T category more strongly predicted overall survival than N category in colon cancer (likelihood chi-square test statistic pT:7009 vs pN:3586). Conclusions: Hierarchy in survival based on AJCC summary stage was not observed for patients with stage II-III colon cancer resulting in a paradoxical better observed survival with some stage III cancer subgroups compared to stage II cancer subgroups. High T category appears to more significantly impact survival than N category for patients with N0-N1 disease, while high N category appears more important for patients with T1-3 disease. Future revisions of the AJCC staging system should account for the differential impact of T and N category identified herein to more accurately confer prognostic information.

Abstract PD4-03: Can genomic profiling eliminate the need for SLNB in ER positive, T1-2 breast cancer?

Abstract Background: As tumor biology has taken precedence over anatomic staging, NCCN guidelines now allow for genomic profiling to make adjuvant treatment recommendations for Nmi-N1 breast cancer (BC). This makes nodal status, determined by sentinel lymph node biopsy (SLNB), less influential. Although generally safe, SLNB adds an incision, operative time, monetary costs, and carries risks of chronic paresthesia (9%) or lymphedema (2-6%). We hypothesized that, if ultrasound (US) excludes occult nodal metastasis and genomic profiling is used in making chemotherapy recommendations for N0-N1 disease, SLNB will be the sole indicator of a need for chemotherapy in &amp;lt;5% of patients. Methods: This was a retrospective data and tissue analysis of patients treated at our breast center (11/2011 – 12/2015). Postmenopausal women with ER positive, HER2 negative, pT1-2 BC with non-suspicious axillary US who underwent SLNB without preoperative chemotherapy were included. For each patient, we compared recommended adjuvant therapy (per NCCN guidelines) based on SLNB results, versus the recommendation had SLNB been negative. For N0-N1 cases, we used Oncotype DX Breast Recurrence Score® test to determine chemotherapy. For Nmi-N1 cases, chemotherapy was considered for Recurrence Score® (RS) 18-25 and recommended for RS &amp;gt; 25. When not in the electronic medical record (EMR), RS result was obtained from stored specimens, with patient consent. Patients without a RS result were excluded from the chemotherapy outcomes analysis. Results: Of 217 included patients, nodal status was as follows: N0, n=184 (85%); Nmi-N1, n=29 (13%); N2-3, n=4 (2%). Therefore, in 85% of patients SLNB did not influence any adjuvant treatment recommendation. In 4.1% of patients, SLNB resulted in a recommendation for axillary lymph node dissection (Table). In 15.2% of patients (n=33), SLNB resulted in a consideration (13.4%) or recommendation for (1.8%) nodal irradiation. RS result was available in 147 patients (68% of cohort). However, only 8 of those with unknown RS result (4% of cohort) were node-positive; for node-negative patients, RS would not affect any study outcome (change in treatment based on SLNB). Among patients with RS result, based on actual SLNB result, chemotherapy was recommended or considered in 30 patients. In 23 of these, chemotherapy would have been recommended regardless of SLNB result based on RS &amp;gt; 25. Therefore, SLNB made a difference in whether to recommend or consider chemotherapy in 4.7% of patients (7/147). Conclusions: SLNB changed the recommendation whether to receive chemotherapy (no to yes, or no to consider) in only 4.7% of patients. More often, SLNB influenced the chemotherapy regimen recommended (2nd vs. 3rd generation), or local therapy recommendations. With increasing role for genomic profiling, the role of SLNB in determining adjuvant therapy is diminishing. When chemotherapy would not be considered, omission of SLNB may be considered in postmenopausal patients with ER positive, T1-2 BC and negative axillary US. If genomic profiling were performed prior to surgery, the results could change surgical management. In women with RS 0-11, SLNB is highly unlikely to alter the recommendation against chemotherapy. In women with RS &amp;gt; 25, chemotherapy is recommended regardless of SLN status, but a positive SLN would affect the regimen recommended. SLNB is most influential in patients with RS 18-25. Use of genomic profiling preoperatively to tailor whether SLNB is performed should be prospectively validated. Table. Comparison of adjuvant treatment recommendations based on SLNB result vs. presumed negative SLNBBased on presumed negative SLNBBased on actual SLNB result% for whom SLNB would change treatment recommendation8Axillary lymph node dissection recommended1094.1% (9/217)Nodal irradiation recommended2041.8% (4/217)Nodal irradiation considered302913.4% (29/217)Chemotherapy recommended423240.6% (1/147)Chemotherapy considered5064.1% (6/147)Third-generation chemotherapy recommended6064.1% (6/147)Third-generation chemotherapy considered7064.1% (6/147)1)For &amp;gt;2 positive SLN, or gross extranodal extension (ENE). Since surgeon determination of gross ENE was not consistently available, &amp;gt; 2 mm of ENE on pathology was used to defined “gross” extension. 2)For N2-3 disease 3)For Nmi-N1 disease 4)For RS &amp;gt; 25, or N2-3 5)For Nmi-N1 disease, with RS 18-25 6)For Nmi-N1 disease with RS &amp;gt; 25; or N2-3; this group is a subset of those for whom chemotherapy would be recommended 7)For Nmi-N1 disease with RS 18-25; this group is a subset of those for whom chemotherapy would be recommended 8)Patients without Recurrence Score result were excluded from analysis of chemotherapy outcomes; fractions are included to show the denominator used for each calculation. Citation Format: Rubie Sue Jackson, Elaine Lee, Carol Tweed, Charles Mylander, Laura Martino, Martin Rosman, Kip Waite, Nicholas Huerta, Lorraine Tafra. Can genomic profiling eliminate the need for SLNB in ER positive, T1-2 breast cancer? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-03.

Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma

PurposeTo assess the impact of tumor necrosis on treatment sensitivity and long-term survival in patients with nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiation therapy (IMRT). Participants and methodsIn total, 757 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients were treated using IMRT; 93.7% patients with stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. ResultsThe incidence rates of tumor necrosis in primary tumor, retropharyngeal lymph nodes, neck lymph nodes, and total tumor were 2%, 17.7%, 21.5%, and 31.4%. Overall, 40.8% patients with necrosis of the total tumor achieved complete response (CR) and 54.7% patients without tumor necrosis achieved CR at the end of treatment (χ2 = 12.728, P < 0.001). The estimated 7-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and loco-regional relapse-free survival (LRRFS) for patients with tumor necrosis and without tumor necrosis of the total tumor were 68.5% vs. 88.4%, 70.5% vs. 88.1%, 77.6% vs. 90.6%, and 85.9% vs. 91.3%, respectively (all P < 0.001). Multivariate analyses indicated that necrosis of the total tumor was an independent predictor of OS, FFS, DMFS, and LRRFS. The impact of lymph node necrosis on long-term survival was similar to that of necrosis of the total tumor. ROC curves verified that inclusion of lymph node necrosis improved the predictive value of the current N classification criteria (P = 0.006). ConclusionsTumor necrosis served as a predictor of treatment sensitivity and poor prognosis for patients with NPC. Lymph node necrosis significantly improved the prognostic value of the current N classification criteria for NPC.

Meta-Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

PurposeConcurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA‐NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta‐analysis investigates the value of adding ICT to CCRT in LA‐NPC.Materials and MethodsTwo reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment‐naive adult patients with histologically proven nonmetastatic LA‐NPC.ResultsEight RCTs with in total 2,384 randomized patients, of whom 69% had N2–N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%–100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) –0.001–0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, −0.243; 95% CI, −0.403 to −0.083; p = .003). Grade 3–4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511–0.905; p = .001) and progression‐free survival (HR, 0.657; 95% CI, 0.568–0.760; p < .001).ConclusionAlthough ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA‐NPC, but further study on optimal patient selection for this treatment is warranted.Implications for PracticeLocally advanced nasopharyngeal carcinoma (LA‐NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta‐analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA‐NPC is associated with a significant clinical improvement in both overall survival and progression‐free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA‐NPC.

Surgery as a Potential Treatment Option for Patients With Stage III Small-Cell Lung Cancer: A Propensity Score Matching Analysis.

Surgery is commonly recommended for patients with stage I small-cell lung cancer (SCLC), whereas chemotherapy and radiotherapy are considered the standard treatment for patients with stage III SCLC. However, recent studies have suggested that a small proportion of patients with SCLC at an advanced stage may benefit from surgical resection. Therefore, in this study, we investigated the effectiveness of surgery in patients with stage III SCLC. Patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2013. Propensity score matching (PSM) was used to eliminate any clinical bias. The overall survival (OS) was determined using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional-hazards model was used to identify the effect of surgery on the OS. Of 9606 patients with stage III SCLC, 234 underwent surgery. Compared with the non-surgical group, a higher proportion of patients undergoing surgery had T1 and N0-N1 disease (risen by 10.7% for T1; 12.6% for N0-N1) and a lower proportion had T4 and N3 disease (decreased by 14.3% for T4; 12.5% for N3). The Kaplan-Meier analysis showed that patients who underwent surgery had a better OS before and after PSM. The multivariate analysis showed that surgery was beneficial for patients with stage III SCLC (HR: 0.651, 95% CI 0.524–0.808, P < 0.001). In conclusion, surgical resection might be associated with improved OS for patients with stage III SCLC and may be considered for the treatment of these patients. Further prospective studies are required to confirm these findings.

Is Proton Therapy a "Pro" for Breast Cancer? A Comparison of Proton vs. Non-proton Radiotherapy Using the National Cancer Database.

Background: Limited data exists demonstrating the clinical benefit of proton radiotherapy (PRT) in breast cancer. Using the National Cancer Database, we evaluated predictors associated with PRT use for patients with breast cancer. An exploratory analysis also investigates the impact of PRT on overall survival (OS).Methods: Patients with non-metastatic breast cancer treated with adjuvant radiotherapy from 2004 to 2014 were identified. Patients were stratified based on receipt of PRT or non-PRT (i.e., photons ± electrons). A logistic regression model was used to determine predictors for PRT utilization. For OS, Multivariable analysis (MVA) was performed using Cox proportional hazard model.Results: A total of 724,492 patients were identified: 871 received PRT and 723,621 received non-PRT. 58.3% of the PRT patients were group stage 0–1. Median follow-up time was 62.2 months. On multivariate logistic analysis, the following factors were found to be significant for receipt of PRT (all p < 0.05): academic facility (odds ratio [OR] = 2.50), South (OR = 2.01) and West location (OR = 12.43), left-sided (OR = 1.21), ER-positive (OR = 1.59), and mastectomy (OR = 1.47); pT2-T4 disease predicted for decrease use (OR = 0.79). PRT was not associated with OS on MVA for all patients: Hazard Ratio: 0.85, p = 0.168. PRT remained not significant on MVA after stratifying for subsets likely associated with higher heart radiation doses, including: left-sided (p = 0.140), inner-quadrant (p = 0.173), mastectomy (p = 0.095), node positivity (p = 0.680), N2-N3 disease (p = 0.880), and lymph node irradiation (LNI) (p = 0.767).Conclusions: Receipt of PRT was associated with left-sided, ER+ tumors, mastectomy, South and West location, and academic facilities, but not higher group stages or LNI. PRT was not associated with OS, including in subsets likely at risk for higher heart doses. Further studies are required to determine non-OS benefits of PRT. In the interim, given the high cost of protons, only well-selected patients should receive PRT unless enrolled on a clinical trial.

Abstract P2-11-24: Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period

Abstract Background: The aim of this study was to identify factors that influence the delivery of post-mastectomy radiotherapy (PMRT) in Switzerland, and to analyze the adherence to consensus guidelines. Methods: Based on 7 regional cancer registries covering 45% of the Swiss population, we identified 1408 women which underwent mastectomy for stage I-III breast cancer between January 1, 2003 and December 31, 2005. We categorized patients according to ASCO grouping in similar fashion to other comparable studies: low-risk group (T1/T2 N0): PMRT not routinely recommended; intermediate-risk group (T1/T2 N1): PMRT controversial; high risk group (T3-T4 and/or N2-N3): PMRT recommended. We further investigated factors leading to potential overtreatment (PMRT in low-risk group) or undertreatment (absence of PMRT in high-risk group). Data analysis was performed for the entire cohort, and separately for patients &amp;lt;70 years and ≥ 70 years of age. Probability of receiving PMRT was assessed using multivariable logistic regression. Results: A total of 421 patients (29.9%) received adjuvant RT after mastectomy. The rate of PMRT delivery was 67% in the high-risk group, compared to 6% and 18% in the low-risk and intermediate-risk groups, respectively. For patients at high-risk of chest wall recurrence after mastectomy (T3-T4 or N2-N3 disease), the risk of PMRT omission wassignificantly associated to older age (OR 4.25 [95% CI: 2.27-7.95] for patients ≥ 70 years) and to the absence of chemotherapy (OR 4.30 [95% CI: 1.97-9.36]). In patients with T3-T4 disease, PMRT was delivered in 77% of patients &amp;lt; 70 years and in 42% of patients ≥ 70 years (p&amp;lt;0.001). In patients with N2-N3 disease, PMRT was delivered in 82% of patients &amp;lt; 70 years and in 51% of patients ≥70 years (p&amp;lt;0.001). PMRT was delivered to 28 patients (7%) at low-risk of recurrence after mastectomy (T1-T2 N0, negative margins). It was more frequently offered to patients &amp;lt;40 years of age (OR 3.86 [95% CI: 1.01-14.76]), with T2 tumors (OR 3.43 [95% CI: 1.45-8.11]) and negative hormone receptor status (OR 2.60 [95% CI: 1.04-6.50]). Positive or close surgical margins (&amp;lt; 1mm) were a strong indicator for PMRT (p=0.001) and chest wall boost (p&amp;lt;0.03). Conclusions: After mastectomy, one third of patients (33.26%) with high-risk disease did not receive PMRT. Even if we consider only patients &amp;lt; 70 years, a non-trivial proportion of patients with clear indication for treatment delivery did not receive PMRT (T3-T4 disease: 23%; N2-N3 disease: 18%). Further analyses are planned to explain the apparent failure of evidence-based guidelines to impact the adoption of PMRT in women with high-risk breast cancer. Citation Format: Zwahlen DR, Ess S, Zimmermann M, Bordoni A, Bouchardy C, Frick H, Konzelmann I, Mousavi M, Rohrmann S, Oehler C. Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-24.

Patterns of Care in Adjuvant Therapy for Resected Oral Cavity Squamous Cell Cancer in Elderly Patients

To characterize the patterns of care and potential barriers to access to care for elderly patients with oral cavity cancer in the adjuvant setting. We performed a retrospective cohort study using the National Cancer Data Base and identified patients with resected oral cavity squamous cell carcinoma diagnosed between 2004 and 2012, who survived for ≥3months after surgery. We used logistic regression models to assess the association between age (<70, 70-79, and ≥80years) and the receipt of adjuvant therapy within 3months of surgery. We additionally assessed the association between patient and tumor characteristics and the receipt of adjuvant therapy among those aged ≥70years. A total of 25,829 patients were included in the study. Compared with those aged <70years, older patients were more likely to have no neck dissection or have fewer lymph nodes dissected and were less likely to receive adjuvant therapy than younger patients. Among our cohort, 11,361 patients (44%) had pathologic T3-T4 disease or N2-N3 disease, and 4185 patients (16%) had extracapsular nodal extension or positive surgical margins. In multivariate analyses controlling for comorbidity and demographic characteristics, older age was independently associated with lower odds of receiving adjuvant radiation therapy in the subgroup with T3 or T4 disease or N2 or N3 disease and adjuvant chemoradiation therapy in the positive extracapsular nodal extension or positive surgical margin subgroup. Among elderly patients, both greater patient distance from reporting facility and older age were associated with lower odds of receiving both adjuvant radiation therapy (odds ratio 0.66; 95% confidence interval, 0.55-0.81) and chemoradiation therapy (odds ratio 0.56; 95% confidence interval, 0.40-0.79). In a national hospital-based cohort of patients with oral cavity cancer, elderly patients were less likely to receive adjuvant radiation or chemoradiation therapy. Greater patient distance from reporting facility, in addition to older age, was associated with lower odds of receiving both adjuvant radiation therapy and adjuvant chemoradiation therapy.

Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS.

Advanced-Stage Nasopharyngeal Carcinoma: Restaging System after Neoadjuvant Chemotherapy on the Basis of MR Imaging Determines Survival.

Purpose To evaluate the prognostic value of the restaging system after neoadjuvant chemotherapy (NACT) in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and Methods This study was approved by the clinical research committee and a written informed consent was required before enrolling in the study. Prospectively enrolled were 412 consecutive patients with stage III-IVb NPC treated with NACT followed by concurrent chemotherapy and radiation therapy. Patients were staged before NACT and restaged after NACT. The progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. Results Post-NACT T classification (PFS, P = .001) and N classification (PFS, P < .001; DMFS, P = .001) resulted in better survival curve separations than pre-NACT T classification and N classification. Patients downstaged from N2-N3 to N0-N1 disease had a better prognosis than did patients who continued to have N2-N3 diseases (3-year PFS, 83.8% vs 66.6%, P = .001; 3-year DMFS, 88.0% vs 78.4%, P = .026). Multivariate analysis revealed that post-NACT T classification (hazard ratio [HR] = 1.67; 95% confidence interval [CI]: 1.18, 2.36; P = .003) and post-NACT N classification (HR = 1.54; 95% CI: 1.17, 2.03; P = .002) were independent prognostic factors for PFS; also, post-NACT N classification (HR = 1.48; 95% CI: 1.05, 2.07; P = .025) was an independent prognostic factor for DMFS. Multivariate analysis in patients with N2-N3 disease demonstrated that the N downstaging effects of NACT was the only independent prognostic factor for PFS (HR = 0.48; 95% CI: 0.29, 0.81; P = .006) and DMFS (HR = 0.52; 95% CI: 0.28, 0.97; P = .039). Conclusion The post-NACT stage is more representative of prognosis than the pre-NACT stage in advanced-stage NPC patients, which suggests that major clinical decisions should be based on the post-NACT stage. © RSNA, 2016 Online supplemental material is available for this article.

Increase in primary surgical treatment of T1 and T2 oropharyngeal squamous cell carcinoma and rates of adverse pathologic features: National Cancer Data Base.

There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features. Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed. Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (odds ratio, 2.23; 95% confidence interval, 1.55-3.22 [P<.0001]). Higher lymph node classification was found to be predictive of lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among patients treated with surgery, positive surgical margins were present in 24% and ECS in 25% of patients. The rate of positive surgical margins decreased over time (P<.0001) and was observed less often at high-volume centers (P<.0001). Among candidates for single-modality therapy (those with clinical T1-T2/N0-N1 disease), 33% had positive surgical margins and/or ECS and 47% had at least 1 adverse feature (T3-T4 disease, N2-N3 disease, positive surgical margins, and/or ECS). Primary surgical treatment among patients with early T classification OPSCC has become more widespread. Cancer 2016;122:1523-32. © 2016 American Cancer Society.

Assessment of the total cfDNA and HPV16/18 detection in plasma samples of head and neck squamous cell carcinoma patients

The advantages of the circulating cell-free DNA (cfDNA) methodology are quick results and the possibility of repeated analysis. The main aim of our study was to establish the relationship of the total cfDNA with patients' clinical characteristics and circulating HPV DNA detection in the blood of patients with head and neck squamous cell carcinoma (HNSCC). The cfDNA level of 200 HNSCC patients in plasma was quantified using TaqMan-based TERT amplification. TaqMan technology was also used for HPV16/18 detection. Additionally, mutations in KRAS and EGFR were investigated. A higher level (p=0.011) of the total cfDNA was found in patients with oropharyngeal squamous cell carcinoma (OPSCC) (9.60 ± 6.23 ng/ml) in comparison with other HNSCC (7.67 ± 4.44 ng/ml). The level of cfDNA in patients with clinical N2-N3 disease (9.28 ± 6.34 ng/ml) was (p=0.015) higher than in patients with a clinical N0-N1 disease (7.50 ± 3.69 ng/ml). It was also higher in patients with stage IV (9.16 ± 6.04 ng/ml) compared with stages I-III of cancer (7.26 ± 3.63 ng/ml) (p=0.011). Analysis of HPV16/18 in plasma revealed that 14% of patients were HPV-positive, the majority of whom had the type HPV16 (96.4%). CfDNA level was comparable in HPV-positive and HPV-negative HNSCC patients, as well in the OPSCC subgroup. Somatic mutations in EGFR and KRAS were not found. A high level of cfDNA is specific for patients with OPSCC. HPV detection in cfDNA does not depend on the cfDNA concentration. Our results prove the diagnostic potential of plasma-based HPV cfDNA tests for the early detection and monitoring of HPV-positive HNSCC.