Higher Rates Of Locoregional Recurrence Research Articles

Oncological outcomes of unexpected uterine leiomyosarcoma: A single-center retrospective analysis of 5528 consecutive hysterectomies.

Uterine leiomyosarcomas (uLMS) are rare malignant tumors, often incidentally discovered, with an estimated annual incidence of five cases per onemillion women in the United States. This study aimed to compare the oncological outcomes of two groups of patients: those with uLMS incidentally found during surgery and those who underwent surgery due to suspected or confirmed uLMS before the procedure. The study assessed patients who had undergone hysterectomy and were diagnosed with stage I uLMS at a tertiary gynecologic oncology referral center in Italy between January 2000 and December 2019. Data on patients'baseline characteristics, surgical procedures, and oncological outcomes were collected. The patients were classified into two groups based on whether uLMS was unexpectedly discovered or suspected before the surgery. Survival rates and factors influencing recurrence were analyzed. The study included 36 patients meeting the inclusion criteria, with 12 having preoperatively suspected or proven uLMSand 24 having incidentally discovered uLMS. No significant differences were observed between the two groups regarding disease-free survival (23.7 vs. 27.3 months, log rank = 0.28), disease-specific survival (median not reached, log rank = 0.78), or sites of relapse. Notably, among patients who underwent laparoscopic hysterectomy (compared to open surgery), a significantly higher rate of locoregional recurrence was found (78% vs. 33.3%, p = 0.04). Nevertheless, no significant differences in survival were observed based on the surgical approach. Preoperative suspicion for uLMS did not seem to impact survival outcomes or the pattern of recurrence. Furthermore, although patients who underwent laparoscopic hysterectomy showed a higher rate of locoregional relapse, this did not affect their overall survival.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer

Purpose/Objective(s)Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. Materials/MethodsWe performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. ResultsMean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). ConclusionLow-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Five Fraction Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer

Accelerated partial breast irradiation (APBI) represents an alternative to whole breast irradiation (WBI), reducing the target volume and potentially treatment duration. APBI delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable outcomes to WBI with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were initially promising, concerns regarding long-term rates of local recurrence exist. We present a comparison of 5 fraction APBI versus IORT. We performed a retrospective review of 473 patients with early-stage breast cancer (Stage 0-IIA) treated at a single institution with 258 receiving APBI and 215 IORT from October 2011 to May 2021. APBI patients received 30 Gy in 5 fractions delivered with IMRT daily or every other day. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery. Kaplan-Meier analysis was used to estimate locoregional control rates and overall survival among the 2 groups. Mean age was 70.7 years old (IQR:67-74) for the IORT patients and 66.6 years old (IQR:62-72) for the APBI patients (p<0.001). Median follow up was 5.7 years for IORT patients and 2.4 years for APBI patients (p<0.001). For IORT patients, 11%/83.5%/5.5% of patients and for APBI 17.8%/77.5%/4.7% of patients had Tis/T1/T2 disease (p = 0.005). With regards to adjuvant therapies, 79%/76% of IORT/APBI patients were offered endocrine therapy (p = 0.50) and 1.4%/6.2% chemotherapy (p = 0.008). Recurrence at any time was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving APBI. APBI was however no differences in recurrence free survival (92.6% vs. 98.5%, p = .079) or overall survival were noted (92.8% vs. 95.1%, p = 0.99). In a series of almost 500 patients with stage 0-IIA breast cancer, IORT was associated with higher rates of locoregional recurrence compared to APBI with no survival difference at 5 years. These outcomes, consistent with other series and current guidelines, suggest a limited role for IORT as monotherapy following breast conserving surgery.

Long-term locoregional recurrence in patients treated for breast cancer.

Locoregional control in breast cancer is a fundamental part of treatment and determinant for survival outcomes. It has been reported that most locoregional recurrence (LRR) events occur in the first 5 years after treatment. However, LRR continue to occur after this timeline, with unclear risk factors and unknown survival impact. Retrospective singe-centered cohort of patients treated for primary breast cancer, between January 2002 and December 2004. Primary outcome was LRR; secondary outcomes were overall survival (OS), disease-free survival (DFS), and predictive factors for LRR. This analysis included 1001 patients, of which 959 (95%) had invasive carcinoma. A mastectomy was performed in 501 (50%) and 500 (50%) had breast conservative surgery (BCS). Median follow-up time was 197 [Inter-quartile range (IQR) 96-211] months. Global LRR rate was 7.6%, with median time to recurrence of 45 [IQR 21-91] months. There was no difference in LRR rate after mastectomy vs BCS, adjusted to tumor stage (p > 0.05). The 10-year OS and DFS rates were 68.4 and 77.8%, respectively. Factors associated with LRR were metastatic axillary lymph nodes and high histologic grade (p < 0.05). Estrogen-negative (ER) tumors had higher LRR rates than ER-positive tumors in the first 5years (p < 0.05); but no difference was observed with longer follow-up (p > 0.05). LRR was associated with OS (p < 0.05). Global LRR in this cohort was 7.6% (with over 16years of follow-up). LRR associates with decreased OS. Time to LRR varies significantly with tumor biology, supporting differentiation of follow-up regimens.

Laparoscopic surgery for rectal cancer, specimen extraction: transanal or transabdominal?

BackgroundComparison of natural orifice specimen extraction (NOSE) and transabdominal specimen extraction (TASE) in colorectal surgery remains controversial. Herein, we aimed to perform a retrospective analysis on surgical outcomes of NOSE and TASE at three hospitals in east of Iran.MethodConsecutive locally advanced rectal adenocarcinoma patients who underwent laparoscopic surgery using either NOSE or TASE from 2011 to 2017 were recruited. These patients were followed-up till 2020. Data, including postoperative complications, long-term overall and recurrence-free survival were analyzed retrospectively.Results239 eligible patients were included in this study. 169 (70.71%) patients underwent NOSE, and 70 (29.29%) patients underwent TASE. Although this study has achieved similar outcomes in terms of overall and recurrence-free survival, metastasis, circumferential margin involvement as well as complications of intra-operative bleeding, obstruction, anastomosis-fail, rectovaginal-fistula in women and pelvic collection/abscess in both groups, we observed higher rates of locoregional recurrence, incontinency, stenosis and the close distal margins involvement in NOSE group and also obstructed defecation syndrome in TASE cases.ConclusionAccording to our findings, NOSE laparoscopic surgery showed significantly higher incontinency, impotency, stenosis and involvement of the close distal margins rates. Nevertheless, considering the similarity of long-term overall and recurrence-free survival, metastasis, circumferential margin involvement, NOSE procedure is still could be considered as a second choice for lower rectal adenocarcinoma patients.

Effect of pre-operative radiation therapy on surgical outcome in retroperitoneal sarcoma.

A high rate of locoregional recurrence is one of the major difficulties in successful treatment of retroperitoneal sarcoma (RPS). Although pre-operative radiation therapy (RT) is considered a potential way to improve local recurrence, concerns about the associated treatment toxicity and risk of peri-operative complications need to be addressed. Hence, this study investigates the safety of pre-operative RT (preRTx) for RPS. A cohort of 198 patients with RPS who had undergone both surgery and RT was analyzed for peri-operative complications. They were divided into three groups according to the RT scheme: (1) preRTx group, (2) post-operative RT without tissue expander, and (3) post-operative RT with tissue expander. The preRTx was overall well tolerated and did not affect the R2 resection rate, operative time, and severe post-operative complications. However, the preRTx group was associated with higher incidence of post-operative transfusion and admission to intensive care unit (p = 0.013 and p = 0.036, respectively), where preRTx was an independent risk factor only for the post-operative transfusion (p = 0.009) in multivariate analysis. The median radiation dose was the highest in preRTx group, although no significant difference was demonstrated in overall survival and local recurrence rate. This study suggests that the preRTx does not add significant post-operative morbidity to the patients with RPS. In addition, radiation dose elevation is achievable with the pre-operative RT. However, a meticulous intra-operative bleeding control is recommended in those patients, and further high-quality trials are warranted to evaluate the long-term oncological outcomes.

Epidemiology, staging and management of mucosal melanoma of the head and neck: a narrative review.

Mucosal melanoma of the head and neck (MMHN) are rare, aggressive neoplasms of melanocyte origin that remain incompletely understood and have a poor prognosis, with high rates of locoregional recurrence and distant metastasis. Several recent studies having expanded understanding of MMHN, we undertook a review of the latest evidence pertaining to its epidemiology, staging, and management. A literature search was conducted for peer-reviewed articles reporting and discussing the epidemiology, staging, and management of MMHN. PubMed, Medline, Embase and the Cochrane Library were searched to identify relevant publications. MMHN remains an uncommon disease. The current TNM staging system for MMHN provides inadequate risk stratification, and consideration of an alternative staging model such as one based on a nomogram may be justifiable. Tumour resection with clear histological margins remains the cornerstone of optimal treatment. Adjuvant radiotherapy may improve locoregional control but does not appear to affect survival. Immune checkpoint inhibitors and c-KIT inhibitors demonstrate promising efficacy in patients with advanced or unresectable mucosal melanomas, and warrant further research exploring the utility of combination therapies. Their roles as adjuvant therapies have not been determined. The efficacy of neoadjuvant systemic therapy is also not yet clear, although early results suggest that it may improve outcomes. New insights into the epidemiology, staging and management of MMHN have transformed the standard of care for this rare malignancy. Nonetheless, the results of ongoing clinical trials and future prospective studies are required to better understand this aggressive disease and optimise its management.

Treatment of rectal cancer after previous prostate cancer: A single institution experience.

Clinical guidelines typically recommend a combination of chemotherapy, radiotherapy and surgery for the management of newly diagnosed rectal cancer. However, standard-of-care treatment may be high risk or not feasible after prior treatment for prostate cancer. Very few case reports describe outcomes or treatment options in this instance. The aim of the present retrospective study was to determine local treatment patterns and outcomes in patients with this diagnosis. The study population consisted of patients with rectal cancer who were treated at Westmead Hospital (Western Sydney, Australia) between January 2008 and January 2020, and had a background of previously treated or synchronous prostate cancer. A review of electronic medical records was conducted and a descriptive analysis was performed. In total, 15 (6.4%) male patients with rectal cancer had a synchronous or previously treated prostate cancer. Stage II, III and IV rectal cancer was recorded in 60.0, 26.7 and 13.3%, respectively. Overall, 8 patients had previously received definitive intent radiotherapy and did not receive neoadjuvant radiotherapy for their rectal cancer. After a median follow-up time of 2.4 years, 25.0% had experienced loco-regional recurrence and the overall survival rate was 87.5%. A total of 3 patients with higher-stage disease underwent neoadjuvant chemotherapy without radiotherapy, resulting in three R0 resections and no recurrences, at the time of data cut-off. At the centre in the present study, prior prostate cancer affected treatment decisions for newly diagnosed rectal cancer. Neoadjuvant chemotherapy was well tolerated and is an option for patients with stage III disease. Outcomes in patients who did not receive neoadjuvant radiotherapy were acceptable but with high rates of loco-regional recurrence. These findings provide some guidance for other clinicians when making decisions regarding treatment of this challenging disease.

Positive clinical outcomes following therapy with programmed cell death protein 1/programmed cell death ligand 1 inhibitors in neuroendocrine carcinoma of the cervix.

Neuroendocrine carcinoma of the cervix (NECC) is a highly aggressive and rare gynecological malignancy with a poor prognosis. Despite aggressive local and systemic treatments, there are high rates of locoregional recurrence and distant metastases. Therefore, more potent treatments are required to manage NECC. In recent years, emerging immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors, have been used in treating various solid tumors and provide a new direction for immune-targeted therapy for NECC. In this review, we summarize the biomarkers useful for the evaluation of the therapy with PD-1/PD-L1 inhibitors in patients with NECC and the clinical applications and prospects of monotherapy with PD-1/PD-L1 inhibitors and combinations with other therapies in patients with NECC. In some individual case reports, therapeutic strategies with PD-1/PD-L1 inhibitors showed good efficacy. Further studies are needed to confirm the possibility of using PD-1/PD-L1 inhibitors as a standard treatment strategy in NECC.

Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer and Ductal Carcinoma In Situ

<h3>Purpose/Objective(s)</h3> Accelerated partial breast irradiation (APBI) delivered with intensity modulated radiation therapy (IMRT) over 5 fractions represents an attractive and convenient method of delivering adjuvant radiation therapy without compromising oncologic or aesthetic outcomes. Intraoperative radiation therapy (IORT) is another method of delivering radiation therapy to the lumpectomy cavity. Initial results reported in clinical trials utilizing IORT were encouraging; however, with longer follow up, higher rates of local recurrence have been observed in contrast to APBI. We report the outcomes of a large cohort of patients treated with 5 fraction APBI and IORT at our institution after undergoing breast conservation surgery (BCS) for stage 0-IIA breast cancer. <h3>Materials/Methods</h3> We performed a retrospective review of 482 patients with stage I-IIA stage breast cancer and ductal carcinoma in situ (DCIS) treated with lumpectomy and APBI at our institution. In total, 267 patients in our cohort received IMRT from December of 2015 to May of 2021 while 215 patients received IORT from October of 2011 to May of 2019. All patients in the IMRT group received 30 Gy in 5 fractions. All patients in the IORT group received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery without additional radiation. Kaplan-Meier analysis was used to estimate locoregional control (LRC) and overall survival (OS) among the 2 groups. <h3>Results</h3> Mean age at diagnosis of the patients was 67 years in the IMRT group and 71 years in the IORT cohort. The IMRT group included 220 patients with Stage I breast cancer (82%), 4 patients with Stage IIA breast cancer (1%), and 43 (16%) patients with DCIS. The IORT group had 198 (92%) with stage I breast cancer, 12 patients (6%) had Stage IIA breast cancer, and 5 patients (2%) had DCIS. After a median follow up of 16 months in the APBI group, only 1 (0.4%) patient experienced a local recurrence, and no patients experienced a regional or distant recurrence. After a median follow up of 55 months in the IORT group, 12 patients (5.6%) experienced a local recurrence, 1 patient (0.5%) experienced a nodal recurrence, and 4 patients (1.9%) experienced a distant recurrence. There was no significant statistical difference in hormonal therapy receipt between both groups (75.3% vs 76.7%, p=0.64). There was no significant difference in 2-year LRC between the APBI and the IORT groups (98.9% in the APBI group vs. 99% in the IORT group, p=0.32). There were no differences in 2-year OS between the two groups (99.6% vs 98.5%, p=0.33). The 5-year LRC was 92.7% in the IORT group. <h3>Conclusion</h3> In a large institutional series of patients with Stage 0-IIA breast cancer treated with BCS followed by 5 fraction APBI or IORT, despite having low risk features and high rates of endocrine therapy use, IORT was associated with high rates of locoregional recurrence of approximately 7% at 5 years. Longer term follow up is needed for comparative effectiveness observations between the two groups.

Tumor-Targeted Injectable Double-Network Hydrogel for Prevention of Breast Cancer Recurrence and Wound Infection via Synergistic Photothermal and Brachytherapy.

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)‐alginate double‐network nanocomposite hydrogel (GPA) embedded with 125I‐labeled RGDY peptide‐modified gold nanorods (125I‐GNR‐RGDY) is fabricated. The double‐network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature‐induced PEGDA polymerization driven by near‐infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double‐network hydrogel possesses a dense polymer network and tightly fixes 125I‐GNR‐RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self‐repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single‐photon emission computerized tomography imaging owing to isotope labeling of loaded 125I‐GNR‐RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue.

There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p=0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p=0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n=7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p=0.004) and the advanced stage was a predictor of DSS (p=0.03). Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. 3 Laryngoscope, 133:1110-1121, 2023.

Patterns of care and survival outcomes for young women treated for early breast cancers in a community hospital system.

e12586 Background: Younger women with breast cancer have relatively poor prognosis and higher rates of locoregional recurrence. Epidemiologic data suggest equivalent survival with mastectomy or breast conserving surgery (BCS) in this population. We analyzed patterns of care and survival outcomes for women aged &lt; 45 years with breast cancer treated at Ascension Macomb Oakland Hospital (AMOH), Ascension St John Hospital (ASJH), and Ascension Providence Hospital (APH). Methods: Between 2006 and 2015 there were 4703 patients treated for breast cancers at AMOH, ASJH, and APH. We identified a subset of 319 patients aged &lt; 45 treated for breast cancers and investigated patients' tumor characteristics, type of surgery, and overall survival by using the Metric database and reviewing patient charts. Kaplan-Meier analysis and log-rank tests together with univariate analysis was done by using SAS for Windows 9.4. Results: With median follow-up of 53 months among living patients, 26 patients had died. African American race was associated with decreased overall survival (log-rank p=0.0031). Factors associated with improved overall survival included AJCC stage grouping (p=0.009), estrogen receptor (p=0.0004) or progesterone receptor positivity (p=0.005), or HER2 negativity (p=0.039). Similarly, survival was different according to grouping cases as luminal A (n=174), luminal B (n=39), basal (n=46), HER2 (n=23) and unknown phenotype (n=37) (P=0.008). Considering all cases 91 were treated with BCS (28.5%) and 228 with mastectomy (71.4%; 113 unilateral and 115 bilateral with or without reconstruction). Conclusions: In this group of young women, overall survival was influenced by stage and breast cancer phenotype as expected. African American race was associated with inferior overall survival. We found high rates of mastectomy with or without reconstruction. In the future comprehensive disease profiling will help to direct decision making.

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India.

BackgroundYoung women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India.Materials and methodsBetween January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35–40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method.ResultsOf total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1–30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups.ConclusionYoung BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.

Predicted Th2 Infiltrate is Associated with Outcome in HPV(-) Head and Neck Cancer.

<h3>Purpose/Objective(s)</h3> We previously showed that immune infiltrate affects treatment response in Head/Neck Cancer (HNC) treated with radiation. Here, we evaluate the effect of predicted tumor infiltrating lymphocytes (TILs) on treatment failure following radiation. <h3>Materials/Methods</h3> Nintey-four human papillomavirus negative (HPV-) HNC patients in the TCGA treated with surgery and adjuvant radiation (PORT) comprised the discovery cohort. Pre-treatment tumors were analyzed using RNA-seq. These data were then used to predict tumor cell type abundance using xCell, which quantifies 64 immune, stroma, and tumor cell abundance from tissue RNA-seq data. Predicted TILs associated with overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) in the discovery cohort were examined in a validation cohort of 102 HPV(-) HNC patients treated with surgery and PORT. All patients in the HPV(-) TCGA cohort with available mutation and gene expression data (n=403) were analyzed as were a separate 40 patient HPV(-) HNC cohort. Significant (MutSig) tumor mutations in cancer genes (OncoKB) were examined for association with predicted Th2 infiltrate. Gene expression significantly different between CD4+ T helper 2 (Th2) high and low tumors were analyzed using ingenuity pathway analysis (IPA) to identify pathways associated with predicted Th2 infiltrate. <h3>Results</h3> Several predicted TILs were associated with outcome, but only predicted Th2 infiltrate was significantly associated with higher rates of LRR in both the discovery (p=4e-3) and validation cohorts (p=9e-3). Predicted Th2 infiltrate was significantly increased in tumors harboring mutations in: CASP8, EP300, HRAS, HLA-A, and ZNF750. IPA using genes significantly (FDR 0.01) associated with predicted Th2 infiltrate identified activation of DDR-related pathways and repression of the tumor microenvironment (TME) pathway in tumors with high predicted Th2 infiltrate. Gene expression within each pathway was used to generate a pathway activation score with positive correlation between predicted Th2 and the BRCA1 in DDR pathway (Pearson R 0.73, p<2.2e-16) and negative correlation with the TME pathway (R= -0.45, p<2.2e-16). Similar patterns were seen in a separate 40 patient cohort, with predicted Th2 infiltrate correlated positively with the BRCA1 in DDR pathway (R=0.77, p=5.6e-9) and negatively with the TME pathway (R= -0.42, p=7.2e-3). <h3>Conclusion</h3> We identified predicted Th2 infiltrate associated with LRR in two homogeneously treated, HPV(-) HNC cohorts. We found that Th2 infiltrate was associated with mutations in genes known to be associated with both poor outcome and modulation of TILs. Finally, predicted Th2 was associated with increased activation of DNA damage response pathways and local repression of immune function in the TME. Thus, Th2 infiltrate may potentially mediate resistance to radiation in HPV(-) HNC.

Development and Validation of the Optimal Circumferential Resection Margin in Pathological T3 Esophageal Cancer: A Multicenter, Retrospective Study.

The clinical significance of circumferential resection margin (CRM) in esophageal squamous cell carcinoma (ESCC) remains unclear. Optimal CRM for predicting the recurrence of pathological T3 ESCC was investigated. Seventy-three patients were retrospectively investigated in the development cohort. Patients were divided into CRM-negative and CRM-positive groups, and clinicopathological factors and survival outcomes were compared between the groups. The cutoff value was validated in another validation cohort (n = 99). Receiver operating characteristic analysis in the development cohort showed the cutoff value of CRM was 600 μm. In the validation cohort, patients in the CRM-positive group showed a significantly higher rate of locoregional recurrence (p = 0.006) and worse recurrence-free survival (RFS) (p < 0.001) than those in the CRM-negative group. Multivariate analysis identified positive CRM as an independent predictive factor for poor RFS (hazard ratio, 2.695; 95% confidence interval, 1.492-4.867; p = 0.001). The predictive value of our criteria of positive CRM for RFS was higher than that of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) criteria. Stratified analysis in the neoadjuvant chemotherapy groups also revealed that the rate of locoregional recurrence was higher in the CRM-positive group than in the CRM-negative group both in the pathological N0 and N1-3 subgroups. CRM of 600 μm can be the optimal cutoff value rather than the RCP and CAP criteria for predicting locoregional recurrence after esophagectomy. These results may support the impact of perioperative locoregional control of locally advanced ESCC.

Abstract P3-21-01: A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction

Abstract Background The rate of Nipple Areolar Complex (NAC) sparing mastectomy with implant reconstruction is rapidly increasing as the Korean National Health Insurance reimbursed reconstructive surgery for breast cancer patients from 2015. However, only a few reports about oncologic safety have been reported in the absence of large-scale data. We have analyzed the oncologic outcomes of all consecutive breast cancer patients who had NAC sparing mastectomy with immediate implant reconstruction. Methods We used the data from prospectively collected clinical data of patients who underwent immediate implant reconstruction after NAC sparing mastectomy at the National Cancer Center between January 2012 and December 2017. Demographics, clinicopathological characteristics and the follow-up results were analyzed. The statistical analysis was done to infer relations between risk factors and oncologic outcomes such as death, distant metastasis or locoregional recurrence. Results: A total of 538 breasts was analyzed in 486 patients. The mean age of the patients was 44.6 years. The mean BMI was 22.48 kg/m2. The number of bilateral cases was 52 (10.7%) and 135 patients (27.8%) had multiple tumors. Median follow-up was 4.5 years. Molecular subtypes were 373 HR(+)/HER2(-) (69.3%), 31 HR(+)/HER2(+) (5.8%), 76 HR(-)/HER2(+) (14.1%) and 35 HR(-)/HER2(-) (6.5%). Chemotherapy was performed in a total of 212 (43.6%) patients, of which 68 (32.1%) were neoadjuvant and 144 (67.9%) were adjuvant purposes. Trastuzumab was administered to 53 (10.9%) of patients whose tumor size are larger than 1cm under guideline of reimbursement. Postoperative radiotherapy was performed in 131 patients (26.9%). Distant metastasis occurred in 20 patients (3.7%), and seven (1.4%) died. Locoregional recurrence occurred in 43 cases (8.0%) of 538 breasts, including 14 nipples (2.6%) and 12 subareolar lesions (2.2%). Analyzing risk factors related to locoregional recurrence, HR(-)/HER2(+) type showed the highest incidence of 11/76 (14.7%) among four subtypes. The incidence was statistically significantly lower in the group that received postmastectomy radiotherapy than in the group that did not. (6/131 (4.6%) vs 37/355 (10.4%), p=0.001). The node negative group who did not have postmastectomy radiotherapy (31/377 (8.2%)) showed a numerically higher incidence than the node positive group (8/121 (6.6%)). Conclusion Our results showed that NAC sparing mastectomy with immediate implant reconstruction had similar oncologic outcome in terms of overall survival or distant metastasis, however the locoregional recurrence was rather high. Even this is remediable problems we would admit that NAC sparing mastectomy is a bit different from traditional mastectomy. In case that we inevitably apply this operation to relatively young women with multifocal breast cancer, careful consideration would be needed. In addition, identifying risk factors of locoregional recurrence and tailored post-operative radiation therapy are expected to improve the disease-free survival of breast cancer. Citation Format: Ji Young You, Eun-Gyeong Lee, Soo Jin Park, Byeong Nam Kim, Seeyoun Lee, Eun Sook Lee, So-Youn Jung, Youngmi Kwon, Yun Ju Kim, Chan Wha Lee, Tae Hyun Kim. A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-21-01.

Abstract P1-13-03: Radiotherapy vs. endocrine therapy for hormone receptor positive early stage breast cancer accounting for endocrine therapy adherence

Abstract Purpose/Objective(s):. Several trials have compared endocrine therapy (ET) alone vs. ET and radiotherapy (RT) in low risk early stage estrogen receptor (ER)-positive breast cancer and have shown that the addition of RT to ET modestly reduces the rate of loco-regional recurrence (LRR) without altering survival. ET may also yield modest reductions in contralateral breast events. ET alone has thus become a standard strategy in select patients. Data evaluating the efficacy of RT alone are scarce. However, the toxicity of ET is not trivial and its effectiveness is dependent upon treatment adherence. As RT courses become ever shorter and safer, a re-evaluation of the strategy of RT alone is warranted. This analysis reports on the treatment outcomes of ER-positive early stage breast cancer treated with adjuvant RT or ET alone at a multi-hospital health system. We hypothesized that adjuvant RT alone would yield loco-regional control comparable to that of ET alone and that ET adherence would influence outcomes. Materials/Methods:. The shared electronic health record of multiple facilities within a university health system was queried to identify women with pathologic T1-2 N0 breast cancer treated with breast-conserving surgery between 2007 and 2016. Data collection included demographic features, tumor characteristics, treatment type, and evidence of LRR. Analysis was restricted to those patients with ER positive disease who underwent either RT alone or ET alone. Five-year LRR were compared across groups using the Kaplan-Meier method. Results:. 240 patients met inclusion criteria. Of these, 86 were treated with RT alone and 154 with ET alone. Patient, tumor and ET variables are listed in the table below. ET adherence and duration information were available for 135 out of 154 patients who received ET alone. Patients who completed 5 years of ET or whose ET was discontinued due to the disease recurrence or death were categorized as ET-adherence (ET-A). Patients who discontinued ET before reaching 5 years due to other reasons were categorized as ET-non adherence (ET-NA). Median ET duration in ET-A was 60 months (range, 15-101 months) and in ET-NA was 13 months (range, 1-54 months). The 5-year rates of LRR for RT alone vs. ET alone were 4.1 % (95% CI 0-8.8) vs. 5.0 % (95% CI 1.1-8.9). The 5-year rates of LRR for ET-A vs. ET-NA were 2.0 % (95% CI 0-4.7) vs. 16.4 % (95% CI 1.1-31.7). While the difference in the LRR rates between RT alone vs. ET-A was not statistically significant (p= .481), ET-NA was associated with significantly higher LRR rate compared to RT alone or ET-A (p&amp;lt;.05). The rate of ET non-adherent rate was 21.4%. Conclusion:. RT yielded LRR equivalent to overall ET and superior to ET non-adherence. For patients with early stage ER+ breast cancer, a prospective randomized trial comparing RT to ET and evaluating quality of life (QoL) is needed. In light of emerging data, a five-day course of RT can be considered as an alternative to five years of ET, and RT should be strongly considered if ET adherence is in doubt. Table 1.Patient, tumor and treatment characteristicsRT alone (n=86)ET alone (n=154)Median follow-up (months)50.6 (1-135)48 (3-114)Age (median)63 (39-91)74 (50-87)StageT176 (88.4%)142 (92.2%)T210 (11.6%)12 (7.8%)HistologyGrade 38 (9.3%)9 (5.8%)+LVI5 (5.8%)3 (2.0%)Endocrine Therapy (ET)ET duration (median, months)-57 (1-101)ET-Adherent-102 (66.2%)ET-Non adherent-33 (21.4%)ET duration not available-19 (12.3%) Citation Format: Seung Won Seol, Travis Pflederer, Lauren Weller, Chelain Goodman, Eric D Donnelly, John P Hayes, Jonathan B Strauss. Radiotherapy vs. endocrine therapy for hormone receptor positive early stage breast cancer accounting for endocrine therapy adherence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-03.

Local Tumor Infiltration and Locoregional Recurrence in Desmoplastic Cutaneous Squamous Cell Carcinoma.

Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective. The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure. Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months. The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p < .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p < .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2-51 mm vs median 4 mm, 1-10 mm; p < .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p < .001). The metastasis rate (16.6% vs 2.3%, p < .001) was increased. The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy

BackgroundTumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT.MethodsA total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT.ResultsThe 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2–3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2–3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.ConclusionsNACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).