Disease-free Survival Estimates Research Articles

Assessment of Predictive Factors for Response to Neoadjuvant Chemotherapy in Breast Cancer

Objectives The early identification of breast cancer patients who will not respond to neoadjuvant chemotherapy is valuable for timely change in management strategies. Reliable clinical and pathological markers predictive of response to treatment have considerable potential for practical clinical use. Our longitudinal study aimed to assess clinical, pathological, and immunohistological factors predictive of chemotherapy response. Material and Methods Thirty Five patients of breast cancer underwent six cycles of Taxotere, Adriamycin, and Cyclophosphamide (TAC) based neoadjuvant chemotherapy (Docetaxel 75 mg/m2, Doxorubicin 50 mg/m2 or Epirubicin 100 mg/m2 and Cyclophosphamide 500 mg/m2) every three weeks followed by surgery. Histopathological response was assessed after surgery. At a follow up of 12 months, association between factors was tested with Fisher exact test, survival analysis was done with Kaplan Meier analysis and significance was tested by log rank test. Results Five patients out of 35 had pathological complete response (pCR). 14.8% of all T4 disease (P = 0.043) and 22.7% of all Estrogen receptor (ER) negative patients had pCR (P = 0.025). Among all patients showing pCR, four patients (80%) had Grade III tumors (P = 0.018) while all five patients had high Ki67 index (P = 0.032). At 12 months, the mean estimated overall survival came out to be 11.6 months. Mean estimated disease free survival was less for patients with pCR (7.2 months) vs. partial response (10.1 months) (P = 0.44). Conclusion Our study concluded that tumors with larger size, higher stage, higher grade, ER negativity and higher proliferation index had better response to chemotherapy but these tumors also had a trend towards early relapse.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.

Final Results of the AIEOP (Associazione Italiana Ematologia/Oncologia Pediatrica) AML 2013 Prospective Randomized Trial in Childhood Acute Myeloid Leukemia (AML)

Background: Treatment of children with newly diagnosed AML is based on induction therapy, followed by consolidation approaches which differ according to the group of risk patients (pts) are allocated to. In this respect, most treatment protocols stratify pts into 3 risk groups, namely standard (SR), intermediate (IR) and high-risk (HR), mainly based on the molecular/cytogenetic characterization and values of measurable residual disease (MRD) at the end of induction therapy. We report the outcomes of 371 pts with de novo AML other than acute promyelocytic leukemia (aged 0-18) enrolled in the randomized trial AIEOP AML 2013 (EudraCT:2014-000652-28). Patients and methods: pts were diagnosed and enrolled in the trial from 06/2015 to 06/2022 at 33 Centers affiliated to the AIEOP group. Main pt characteristics and criteria used for stratification are shown in Table 1. A marker of recurrent molecular lesions was detected at diagnosis for 247 cases out of the 371 enrolled (67%). Monitoring of flow-cytometry MRD at the end of the 1 st and 2 nd induction course was centrally performed in all pts but 7. The 1 st induction course was common for all pts (ICE scheme), while, then, SR pts were treated with 4 additional chemotherapy courses, all including high-dose cytarabine (HD-Ara-C). IR and HR pts were randomized to receive either a 2 nd ICE or the FLA-Liposomal Doxorubicin (L-Doxo) scheme as 2 nd induction course. IR pts were given 3 additional consolidation courses including HD-Ara-C with other agents or, in the presence of an HLA-compatible sibling, 1 consolidation course followed by allogeneic hematopoietic stem cell transplantation (HSCT). Pts of the HR group were consolidated with 2 courses of HD-Ara-C combined with other cytotoxic agents and, then, had an indication to receive HSCT from either a donor compatible for &amp;gt; 9/10 HLA loci or from an HLA-partially matched relative. Data cut-off for the analysis was March 31, 2023. Results: The proportion of pts allocated to the SR, IR and HR groups were 19% (72 pts), 23% (81 pts) and 58% (218 pts), respectively. Overall, 92% of pts obtained morphological complete remission (CR) at the end of the 2 induction courses [as compared to 87% of the previous AIEOP AML 2002 study (Pession et al. Blood 2012), p&amp;lt;0.05]. Twenty-five pts (7%) experienced a primary induction failure. Only 3 pts died during or after the 2 induction courses, while the subsequent cumulative incidence of 3-yr non-relapse mortality in continuous CR was 6.8%. Leukemia recurrence occurred in 63 pts, this leading to a 3-yr cumulative incidence of relapse of 18.9%. With a median follow-up of 4.5 yrs (range 0.8-8), the 3-yr probabilities of overall (OS) and event-free survival (EFS) were 83.9% and 68.5% (Figure 1), respectively, both values being significantly better (p&amp;lt;0.01) than those of the AIEOP AML 2002 study. The 3-yr OS of SR, IR and HR pts were 99.2%, 84.2% and 79.4%, respectively (p=0.01). The 3-yr estimate of disease-free survival (DFS) was 74.3%, with no difference among the 3 risk groups. The EFS did not differ in IR and HR randomized to receive either a 2 nd ICE or the FLA-L-Doxo scheme as second induction course. Levels of flow-cytometry MRD after the 2 nd induction course strongly influenced the probability of EFS which was 76% and 48% in pts with an MRD value &amp;lt; or &amp;gt;0.1%, respectively (p&amp;lt;0.01). Allogeneic HSCT was performed in 160 pts; in these pts, the 3-yr probabilities of OS and DFS were 87.7% and 85.1%, respectively, with no difference according to the type of donor employed. The DFS of the 10 IR pts given HSCT was 100% as compared to 72.1% of the 71 not transplanted (p=0.07). The outcome of infants treated in this study was particularly good, since their 3-yr probability of EFS was 78.3%. The 3-yr EFS of the 35 pts with FLT3-ITD and of the 75 with KMT2-A rearrangements were 57.1% and 64.7%, respectively. Conclusions: These results indicate that in children enrolled in the trial AIEOP AML 2013 the 3-yr OS and EFS overcomes 80% and approaches 70%, respectively, with a significant improvement as compared to the previous AIEOP protocol. Disease recurrence/primary resistance were the main cause of treatment failure, while the probability of DFS did not differ among the 3 different risk groups, this finding indicating that tailoring of consolidation therapy according to the risk profile was successful in improving the outcome of pts with worse prognostic characteristics. The use of FLA-L-Doxodid not offer any advantage over repeating a 2 nd ICE.

Long-Term Follow up for SWOG 1318: Combination of Dasatinib, Prednisone, and Blinatumomab for Older Patients with Philadelphia-Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL)

Tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Many older patients (pts) are not good candidates for intensive chemotherapy and are treated with TKIs plus corticosteroids or low-intensity chemotherapy. Although the remission rates with this approach have been high, the median disease-free survival (DFS) has been short. Therefore, novel treatment strategies are needed. This trial evaluated the feasibility of combining the TKI dasatinib with prednisone and blinatumomab in older pts with Ph+ ALL. Here we present updated results (median follow-up, 4.3 years). Methods: This trial was activated through the NCTN in January 2015 and closed to accrual in April 2021. Pt eligibility included: age ≥ 65 years; Ph+ or Ph-like ALL (with dasatinib-sensitive fusions or mutations); newly diagnosed or relapsed/ refractory; no evidence of central nervous system (CNS) disease; and adequate organ function. Treatment: For induction, pts received dasatinib 140 mg/d orally (PO) Days 1-56 along with prednisone 60 mg/m 2/d PO Days 1-24. Pts achieving complete remission (CR) or CR with incomplete count recovery (CRi) (Day 28 or Day 56) continued dasatinib until Day 84, followed by 3 cycles of post-remission therapy (PRT) with blinatumomab/ dasatinib. Pts not achieving CR or CRi by Day 56 received re-induction with blinatumomab. The response rate was assessed on Day 35 of blinatumomab. Pts not achieving CR/ CRi could receive a second cycle of blinatumomab. This was followed by 3 cycles of PRT with blinatumomab/ dasatinib. Maintenance therapy consisted of prednisone 60 mg/m 2/d x 5 days every 28 days for a total of 18 cycles, along with dasatinib 140 mg po qd indefinitely. CNS prophylaxis included intrathecal (IT) methotrexate every 4-6 weeks x 8 doses. IT methotrexate was given at least 2 days apart from blinatumomab. Response was assessed at Days 28, 56, and 84, and additional time points were dependent on response. Minimal residual disease (MRD) was assessed centrally by multi-color flow cytometry on Day 28. Statistics: A total of 24 eligible patients were accrued. The primary objective was the feasibility of the combination therapy. The combination was to be deemed feasible if the dose-limiting toxicity (DLT) was &amp;lt; 33%. DLT included: &amp;gt; Grade 3 non-hematologic toxicities (excluding nausea, vomiting, diarrhea) and Grade 4 neutropenia lasting &amp;gt; 42 days. The primary results were reported in 2022 with a median of 2.7 years of follow-up. Herein, we report long-term outcomes for these patients. Results: The median age was 73 years (range 65-87). All pts had newly diagnosed Ph+ ALL; 79% of Ph+ pts had additional cytogenetic abnormalities. During induction, 2 pts experienced treatment-related non-hematologic Grade 4 toxicities. No Grade 4 or higher treatment-related non-hematologic toxicities occurred during post-remission therapy or maintenance. The toxicity of the combination was deemed acceptable. Twenty-two of 24 pts (92%) achieved a CR during dasatinib and prednisone induction therapy. Four did not receive PRT (2 due to adverse events, 1 to receive a transplant, and 1 because of insurance issues). Sixteen pts who achieved CR had MRD data. Six of 16 pts (38%) were MRD undetectable by multi-color flow cytometry on Day 28. Most sites also monitored patients' blood or bone marrow with real-time quantitative PCR to quantify the BCR-ABL1 transcript for molecular response. Of 19 patients analyzed, 17 (89%) were in a major or complete molecular remission at some time point after treatment, with at least 12 of these patients achieving complete molecular remission. Four patients remain on maintenance. The median follow- up for pts who are alive is 4.3 years (range 2.6-6.5 years). The median overall survival (OS) is 6.5 years (95% CI 3-NA) and the median DFS has not been reached as of June 29, 2023. Kaplan-Meier 3-year estimates of OS and DFS are 75% (95% CI 52%-88%) and 72% (95% CI 49%-87%), respectively (Figure). Of the 8 relapses, 4 patients were CD19+ and 3 had T315I mutations. Conclusions: Median DFS and OS with dasatinib and blinatumomab in this older group of Ph+ ALL patients remain excellent despite only 1 patient proceeding to an allogeneic transplant. Further correlative studies (single cell transcriptomics and DNA methylation sequencing) are being planned to evaluate predictors of relapse and will be presented at the meeting.

Neoadjuvant Stereotactic MR-Guided Ablative Radiation Therapy (SMART) and Surgical Outcomes in Patients with Pancreatic Cancer

The benefit of neoadjuvant radiation therapy for patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Stereotactic MR-guided adaptive radiation therapy (SMART) treatment to ablative doses is a newer technique that is well tolerated and has increased local control in unresectable pancreatic cancer. For resectable pancreatic cancer, neoadjuvant SMART has the potential to decrease local recurrence risk and positive margin rates. However, there is concern for perioperative risks associated with ablative dose treatments. We report the efficacy and safety of surgical resection in patients who have received neoadjuvant SMART at our institution. We conducted a retrospective analysis of all consecutive patients diagnosed with PDAC who had noted vascular involvement of the celiac axis, superior mesenteric, and/or portal vessels between January 2016 and December 2022 at a single, high-volume, academic institution. Perioperative events were defined according to the Clavien-Dindo classification. The Kaplan Meier method was applied to estimate disease free survival (DFS) and overall survival (OS). Seventeen patients with PDAC and vessel involvement at time of diagnosis who received SMART were included. Median follow-up time was 14.3 months; all patients underwent surgery, at a median time after radiation of 28 days (range: 15 - 90). Median length of postoperative stay was 7 days (range: 3 - 15). Five patients (29%) underwent vascular resection. Fifteen patients (88%) achieved R0 resection, with two R1 resections noted at the SMA and pancreatic neck respectively. Seven patients (41%) had adverse events attributable to surgery, with the majority being defined as abscess or infection (n = 5; 29%). One (6%) Clavien-Dindo grade III or higher toxicity was observed - a cortical cerebrovascular event following surgery. No major bleeding events requiring surgical intervention were noted. At time of event censorship, there were no observable locoregional failures. The median DFS and OS were not reached; however, 1-year DFS and OS were 62% and 87%, respectively. Neoadjuvant SMART appears to be safe, with low rates of surgical complications and promising outcomes. Further identification of patients for this approach requires additional investigation.

Multicenter Survival Analysis and Application of an Olfactory Neuroblastoma Staging Modification Incorporating Hyams Grade

Current olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence. The primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence. This retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers. Standard-of-care ONB treatment. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction. A total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18). The study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.

Impact of perioperative chemotherapy on survival in patients with cholangiocarcinoma undergoing curative resection

BackgroundMost patients with localized cholangiocarcinoma (CCA) endure cancer relapse after curative resection underscoring the importance of systemic therapy. The current study attempts to determine the impact of perioperative chemotherapy (PC) on survival in patients with CCA undergoing resection. MethodsPatients diagnosed with CCA undergoing curative-intent resection between January 1, 2000, and December 31, 2019, in a tertiary care center were included. Cox proportional hazard modeling was used to determine the impact of PC on disease-free survival (DFS) and overall survival (OS). In addition, a nomogram was constructed to estimate 3-year DFS. ResultsAmong the 182 patients included in the analysis, 102 underwent surgery alone, and 80 received surgery plus PC. Forty-two patients received neoadjuvant therapy, and 38 patients received adjuvant therapy. On multivariate analysis, PC was significantly associated with an improved DFS (HR, 95% CI: 0.63, 0.41–0.98; p = 0.04) and OS (HR, 95% CI: 0.46, 0.27–0.78; p < 0.01). In the interaction analysis, the survival benefit was especially seen in patients with positive resection margins and tumor size > 5 cm. ConclusionIn patients with CCA undergoing curative resection, receipt of PC was associated with improved DFS and OS. The nomogram constructed from this database provides an estimate of 3-year DFS after surgical resection. Randomized trials are needed to define the optimal regimen and sequence.

Parathyroidectomy and the Risk of Major Cerebrovascular and Cardiovascular Events in the Elderly.

We aimed to determine the incidence of major cardiovascular and cerebrovascular events in elderly patients with primary hyperparathyroidism (pHPT) and the impact of parathyroidectomy. pHPT is underdiagnosed and undertreated in the United States. It is associated with increased cardiovascular disease risk, but its association with cerebrovascular disease risk is not well-established. It is also unknown if parathyroidectomy reduces these risks. The incidence of major cerebrovascular and cardiovascular events in 108,869 patients with pHPT diagnosed in the Medicare database between 2008 and 2018 and a matched comparison group of 1,088,690 Medicare subjects was prospectively evaluated. We estimated hazard ratios (HR) for the association of pHPT and parathyroidectomy for the risk of these outcomes from Cox proportional hazards models. Survival curves were calculated to obtain 5-year disease-free survival estimates. For patients with pHPT, five-year disease-free survival was lower, and HRs were higher than the comparison group for any outcome (75.9% vs. 78.4; HR 1.11, 95% confidence interval [CI] 1.09-1.13), major cerebrovascular events (84.5% vs. 86.3%; HR 1.14, 95% CI 1.12-1.17), and major cardiovascular events (87.7% vs. 88.8%; HR 1.06, 95% CI 1.03-1.08). However, in patients who had parathyroidectomy, the risks of major cerebrovascular and cardiovascular events did not differ from the comparison cohort. The lower risk in patients who had parathyroidectomy was maintained in subgroup analyses. Older patients with pHPT have an increased risk of major cerebrovascular and cardiovascular events compared with patients without the disease. Physicians treating older patients with primary hyperparathyroidism should consider parathyroidectomy.R.M.P. and N.N. contributed equally to the preparation of this manuscript.

Long-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.

Cancer Control, Toxicity, and Secondary Malignancy Risks of Proton Radiation Therapy for Stage I-IIB Testicular Seminoma

This study's objective was to report cancer control and toxicity outcomes after proton radiation therapy (RT) in testicular seminoma and to compare secondary malignancy (SMN) risks with photon-based treatment alternatives. Consecutive patients with stage I-IIB testicular seminoma treated with proton RT at a single institution were retrospectively analyzed. Kaplan-Meier estimates for disease-free and overall survival were computed. Toxicities were scored using Common Terminology Criteria for Adverse Events version 5.0. Photon comparison plans, including 3-dimensional conformal RT (3D-CRT) and intensity modulated RT (IMRT)/volumetric arc therapy (VMAT), were created for each patient. Dosimetric parameters and SMN risk predictions for different in-field organs-at-risk were compared between the techniques. Excess absolute SMN risks were estimated with organ equivalent dose modeling. Twenty-four patients were included (median age, 38.5 years). The majority of patients had stage II disease (IIA, 12 [50.0%]; IIB, 11 [45.8%]; IA, 1 [4.2%]). Seven (29.2%) and 17 (70.8%) patients had de novo and recurrent disease, respectively (de novo/recurrent: IA, 1/0; IIA, 4/8; IIB, 2/9). Most acute toxicities were mild (grade 1 [G1], 79.2%; G2, 12.5%) with G1 nausea being most common (70.8%). No serious events (G3-5) occurred. With a median follow-up time of 3 years (interquartile range, 2.1-3.6 years), 3-year disease-free and overall survival rates were 90.9% (95% confidence interval,68.1%-97.6%) and 100% (95% confidence interval, 100%-100%), respectively. There were no documented late toxicities in the follow-up period, including worsening serial creatinine levels suggestive of early nephrotoxicity. Proton RT had significant reductions in mean organ-at-risk doses to the kidneys, stomach, colon, liver, bladder, and body compared with both 3D-CRT and IMRT/VMAT. Proton RT had significantly lower SMN risk predictions compared with 3D-CRT and IMRT/VMAT. Cancer control and toxicity outcomes using proton RT in stage I-IIB testicular seminoma are consistent with existing photon-based RT literature. However, proton RT may be associated with significantly lower SMN risks.

Postoperative Adjuvant Treatment in Women with Stage I Endometrial Cancer: A Retrospective Study.

To evaluate whether postoperative adjuvant treatment is beneficial for patient survival after surgery for early stage endometrial cancer (EC). We analyzed the outcomes of patients treated with radiotherapy, chemotherapy, or progestagen combined with other adjuvant treatments. We analyzed the outcomes of patients treated with radiotherapy alone, chemotherapy alone, or progestagen treatment with other adjuvant treatments. Women without any adjuvant treatment after operation were used as controls. We retrospectively examined disease-free survival (DFS), overall survival (OS), and high-risk factors that affected the survival status of all patients who received different postoperative adjuvant therapies. In all 192 patients, the total relapse and mortality rates were 5.57% and 1.68%, respectively. Fourteen patients (7.29%) developed isolated local recurrence, and 2 patients died (1.04%) of recurrence during the follow-up period. The 5-year DFS and OS rates of all patients were 95.83% and 93.75%, respectively. No significant differences were observed in the 5-year DFS, 5-year OS, OS, or DFS among the four groups of patients with FIGO stage I endometrial cancer (P=0.9849, 0.7430, 0.9754, and 0.4534, respectively). The differences in the log-rank test results of the estimates of the 5-year DFS, 5-year OS, DFS, and OS of patients with different disease stages and different ages were all significant, but no differences were observed in these parameters among patients with varying degrees of differentiation. Histologic grade, CA125 level, ER and PR status, and adjuvant therapy had no significant effect on the DFS and OS of all patients according to univariate and multivariate regression analyses, but a significant effect on DFS and OS was found when the patients were stratified by age. This retrospective study showed that adjuvant therapy after surgery was not significantly associated with improved DFS or OS in patients with early stage endometrial cancer. However, FIGO stage and age affected the survival of patients with stage I endometrial cancer.

Splenic flexure cancer survival: a 25-year experience and implications for complete mesocolic excision (CME) and central vascular ligation (CVL).

The management of splenic flexure cancers (SFCs) in the era of complete mesocolic excision (CME) and central vascular ligation (CVL) is challenging because of its variable lymphatic drainage. This study aimed to compare survival outcomes for SFCs and non-SFCs, and better understand the clinicopathological characteristics which may define a distinct SFC phenotype. An observational cohort study at Concord Hospital, Sydney was conducted with patients who underwent resection for colon adenocarcinoma (1995-2019). Clinicopathological data were extracted from a prospective database. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. Of 2149 patients with colon cancer, 129 (6%) had an SFC. The overall 5-year OS and DFS rates were 63.6% (95% CI 62.5-64.7) and 59.4% (95% CI 58.3-60.5), respectively. SFCs were not associated with OS (P = 0.6) or DFS (P = 0.5). SFCs were more likely to present urgently (P < 0.001) with obstruction (P < 0.001) or perforation (P = 0.03), and more likely to require an open operation (P < 0.001). These characteristics were associated with poorer survival outcomes. No differences were noted between SFCs and non-SFCs with respect to tumour stage (P = 0.3). SFCs have a distinct phenotype, the individual characteristics of which are associated with poorer survival. However, the survivals of SFCs and non-SFCs are similar, possibly because the most important determinant of outcome, tumour stage, is no different between the groups. This may have implications for the surgical approach to SFCs with respect to standardization of CME and CVL surgery for these cancers.

Abstract P6-01-13: Identification of Protein Biomarkers for Early Detection and Stratification of Triple Negative Breast Cancer

Abstract Breast cancer (BC) is the most frequent malignancy in women worldwide. Breast cancer affects roughly 3,000,000 people worldwide, with triple negative breast cancer (TNBC) accounting for 10-15% of all cases. In comparison to other types of breast cancer, TNBC stands out for its heterogenies disease, poor prognosis and aggressive behaviour. In the early stages of TNBC, neoadjuvant chemotherapy (NAC), which is given to the patient before surgery, has been considered a viable treatment strategy. Pathological complete response (pCR), which has been shown to increase estimates of disease-free (the amount of time following treatment during which there are no signs of malignancy), distant recurrence-free (the cancer has spread to far-off regions of the body) and overall survival, has been linked to NAC in 30% of patients. The objective of this study was to apply mass-spectrometry-based proteomics to serum samples from TNBC patients who have received NAC to identify i) biomarkers that might predict response to NAC, ii) biomarkers that might correlate with the extent of residual disease. These biomarkers will potentially inform treatment decisions such as the escalation/de-escalation of chemotherapy dosage for early TNBC patients. In this study, two proteomic approaches have been used to identify and measure protein candidate biomarkers: un-biased LC-MS/MS and targeted proteomics respectively. The discovery approach led to the identification of 17 unique proteins and 118 unique peptides that were differently expressed. The developing of a multiple reaction monitoring (MRM) assay for biomarker evaluation will be based on the prioritization of the potential signature proteins and other proteins obtained from public resources. Subject to successful evaluation and subsequent validation the candidate biomarkers may be beneficial for identifying TNBC patients who will achieve residual disease after NAC. Citation Format: Essraa metwali, Stephen Pennington. Identification of Protein Biomarkers for Early Detection and Stratification of Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-13.

Characterization of GATA3 and Mammaglobin in breast tumors from African American Women

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.

Treatment Outcomes of Adenoid Cystic Carcinomas of the Head and Neck Region-A Single-Institution Experience.

Malu RafiObjectives This study was undertaken to evaluate the characteristics and treatment outcomes of patients with adenoid cystic carcinomas of the head and neck region treated at a tertiary cancer center in south India. Materials and Methods This was a retrospective study done on patients treated at the institute between 2004 and 2011. Clinicopathological details and treatment outcomes were captured from the treatment records to estimate the treatment outcomes and factors affecting them. Results There were a total of 140 patients with mean age of presentation of 46 years and a median follow-up of 65 months. The most common single site of presentation was the oral cavity. One-hundred eighteen patients (84.3%) underwent primary surgical resection in which 38% had negative surgical margins. Ninety-nine patients were given adjuvant radiotherapy and 18 patients received radical radiotherapy, mostly for surgically inaccessible and inoperable tumors. Median time to recurrence and distant metastasis was 37 and 34 months, respectively. The overall survival and disease-free survival estimate using the Kaplan-Meier method were 92.3 and 71.9%, respectively, at 5 years. Surgical removal of the primary tumor and the nodal stage had the most significant impact on the overall survival outcomes of these patients. Conclusion Surgery remains the most impactful treatment modality in the management of these rare epithelial tumors. The use of adjuvant radiotherapy may help to tackle the issues of perineural spread and inadequate surgical margins in technically difficult sites. Radical radiotherapy also has impressive response rates.

Disease-free survival does not differ according to fertility preservation technique for young women with breast cancer

To study whether fertility preservation strategies using ovarian stimulation or without using it impact long-term disease-free survival of patients with breast cancer. Retrospective bicentric cohort study. Two university hospitals. In this study, 740 women with breast cancer, aged 18-43 years, who received primary fertility preservation between 2013 and 2019 after a diagnosis of localized breast cancer were included. Overall, 328 patients underwent at least 1 ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (no STIM group). Disease-free survival and overall survival up to May 2021 were compared between the 2 groups by log-rank test. Cox proportional-hazard regression model was used for multivariable analyses. Out of the 740 women who underwent fertility preservation, follow-up data were available for 269 women in the STIM group (82%) and 330 (80%) in the no STIM group. Kaplan-Meier estimates of disease-free survival at 4 years were 87.9% (82.8%-92.2%) and 83.1% (78.4%-87.3%) in the STIM and no STIM groups, respectively. After adjustment on prognostic parameters, no significant difference in breast cancer recurrence rate was observed between the STIM and no STIM groups (hazard ratios, 0.83 [0.64-1.08]). Kaplan-Meier estimate of overall survival at 4 years was 97.6% (95.3%-99.2%) and 93.6% (90.9%-95.9%) in the STIM and no STIM groups, respectively. Overall survival was higher in the STIM group than no STIM group (log-rank test). After adjustment on prognostic parameters, the risk of death remained significantly lower in the STIM group (Hazard Ratio, 0.55 [0.35-0.85]). In our cohort, STIM for fertility preservation in breast cancer did not significantly impact disease-free survival but was associated with higher overall survival. The disease-free survival and overall survival of young patients with breast cancer were not impacted by fertility preservation techniques irrespective of the timing of chemotherapy (neoadjuvant or adjuvant) and the use of ovarian stimulation. Nevertheless, because death and recurrence were rare events, these results should be taken with caution.

Expression of c-MET in Estrogen Receptor Positive and HER2 Negative Resected Breast Cancer Correlated with a Poor Prognosis.

Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14−54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with high c-MET tumor had significantly worse (p = 0.00026) and BCSS (p = 0.0013). Univariate analysis showed a significant association between large tumor size, elevated Ki67, c-MET values and increased risk of recurrence or death. The multivariate COX regression model showed that tumor size and high c-MET expression were independent predictors of DFS (p = 0.019 and p = 0.022). Moreover, large tumor size was associated with significantly higher risk of cancer related death at multivariate analysis (p = 0.017), while a trend towards a poorer survival was registered in the high c-MET levels cohort (p = 0.084). Conclusions: In our series, high c-MET expression correlated with poor survival outcomes. Further studies are warranted to validate the clinical relevance and applicability of c-MET as a prognostic factor in ER+/HER2- early BC.

Oncologic outcome in patients with 2018 FIGO stage IB cervical cancer: Is tumor size important?

To evaluate the prognostic factors and oncologic outcome in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer (CC) after radical hysterectomy and lymphadenectomy. This study included 290 patients with type II or III radical hysterectomy + pelvic ± para-aortic lymphadenectomy and 2018 FIGO stage IB1-3 epithelial CC. Disease-free survival (DFS) estimates were determinate by using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Multivariate analysis was performed using a Cox proportional hazards models. The mean age of study cohort was 52 ± 10.25 years. Five-year DFS was 93% in entire cohort. On univariate analysis, surgical border involvement (p=0.007), lymphovascular space invasion (LVSI) (p=0.040), uterine involvement (p=0.040), and depth of cervical stromal invasion (p=0.007) were found to have statistical significance for DFS. However, none of them were independent prognostic factors for the risk of recurrence. Tumor size according to 2018 FIGO staging criteria was not related with recurrence. Surgical border involvement, LVSI, depth of cervical stromal invasion, and uterine involvement were predictors for DFS on univariate analysis. Tumor size was not predicting to recurrence in patient with 2018 FIGO stage IB1-3 CC.

Postoperative Radiotherapy for Completely Resected Thymoma: What Can We Learn in the Precision Radiation Era?

<h3>Purpose/Objective(s)</h3> The optimal role of radiotherapy (PORT) after complete thymectomy for thymoma remains controversial. We investigate the role of postoperative radiotherapy in the complete resection of Masaoka-Koga stage Ⅱ/Ⅲ thymoma with precision radiotherapy techniques. <h3>Materials/Methods</h3> From January 2000 to December 2017, patients with Masaoka-Koga stage Ⅱ/Ⅲ thymoma who underwent complete resection or complete surgical resection and underwent radiotherapy with precision techniques were included and analyzed. Clinical, pathological, therapeutic and follow-up information was collected. Kaplan-Meier estimates of overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS), and univariate and multivariate Cox proportional hazards regression analyses were performed. <h3>Results</h3> A total of 244 patients met the selection criteria, 142 (58.1%) of whom were received PORT. Of these, 172 (70.5%) patients with stage Ⅱ thymoma, 72 patients (29.5%) with stage Ⅲ. The median follow-up was 76 months. The 5-year and 10-year OS in the surgical and PORT groups were 93.8% vs 95.4% and 83.6% vs 86.9%, respectively (p=0.34), while the DSS was 93.8% vs 99.0% and 86.3% vs 93.9%, respectively (p=0.038), and the DFS was 85.0% vs 76.9% and 75.9% vs 65.5%, respectively (p=0.65). In stage Ⅲ patients,5-year and 10-year OS was 83.0% vs 95.8%, 54.4% vs 84.4% (HR 0.31, p=0.038) and DSS was 83.0% vs 97.6%, 54.4% vs 91.8% (HR 0.14, p=0.002) for surgery alone vs the PORT group. On multivariate analysis, stage Ⅲ was associated with poorer OS (HR 2.36, <i>p</i>=0.045) and DSS (HR 3.61, <i>p</i>=0.020), and PORT were associated with better DSS (HR=0.26, <i>p</i>=0.012). <h3>Conclusion</h3> Masaoka-Koga stage Ⅱ/Ⅲ thymoma complete resection after radiotherapy with precision radiotherapy techniques resulted in improved DSS but not significant improvement in OS and DFS; Subgroup analysis showed a more pronounced benefit of PORT in stage Ⅲ patients, with benefits in DSS and OS, suggesting that postoperative radiotherapy can be beneficial in more advanced thymoma.

Clinical Outcomes Following Definitive 3D Image-Guided HDR Intracavitary Brachytherapy for Medically Inoperable Endometrial Cancer

<h3>Purpose/Objective(s)</h3> Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S. Brachytherapy alone or in combination with external beam radiation therapy (EBRT) is considered an alternative definitive treatment for women who are not surgical candidates, though limited data exists for outcomes with modern 3D image-guided brachytherapy. As the U.S. population ages and rates of obesity and other comorbidities rise, more women may require definitive radiation therapy. In this study, we report outcomes for a large cohort of patients treated with intrauterine brachytherapy with 3D CT-guided planning. <h3>Materials/Methods</h3> Retrospective review identified 59 women with EC who received high dose rate (HDR) intrauterine brachytherapy with dual or triple tandem applicators with definitive intent, alone or in combination with EBRT, between 2009-2020. All patients underwent endometrial biopsy and 92% had pretreatment diagnostic CT and/or MRI imaging. 3D CT-guided brachytherapy planning was done using planning software. Local failure-free survival (LFFS), disease-free (DFS), and overall survival (OS) estimates were calculated by Kaplan-Meier method. Median follow-up was 44 months (interquartile range [IQR], 17-88). <h3>Results</h3> Median patient age was 68 years (range, 37-87). Patients had atypical complex hyperplasia (15%), or clinical stage I (76%), II (5%), or III (3%) EC. Patients were ineligible for surgery due to medical comorbidities, including obesity (97% of patients), pulmonary disease (36%), cardiovascular disease (41%), renal disease (9%), or complicated prior surgical history (9%). Median BMI was 45.7 kg/m² (range, 17.2-79.7), and 64% of patients met criteria for severe obesity (≥40 kg/m²). Brachytherapy dose delivered ranged from 8.5Gy in 1 fraction to 36.5Gy in 5 fractions. Among patients receiving brachytherapy alone, 83% were treated with 34Gy in 4 fractions. 20% of patients underwent EBRT immediately prior to or following brachytherapy and received lower doses of brachytherapy. Median coverage of the uterus CTV V100 = 92% (range, 65%-99%). 5-year LFFS, DFS, and OS rates were 91%, 82%, and 75%, respectively. Median time to any failure was 15 months (IQR, 10-26). Among 59 patients, 4 failed locally, 3 failed in the peritoneum, and 2 failed both locoregionally and distally. Two of 4 patients who failed locally were successfully salvaged with surgery. Five patients died of EC. Ten patients (17%) had perforation of the uterus with applicator placement. Antibiotics were not given prophylactically and no patients developed bacterial peritonitis or other infectious complication. There was no correlation between perforation of the uterus at the time of brachytherapy and peritoneal spread of EC. <h3>Conclusion</h3> Outcomes following definitive 3D image-guided brachytherapy were excellent, with 5-year LFFS of 91% and 5-year DFS of 82%. Patients rarely died of EC. Our data supports the use of 3D brachytherapy as definitive therapy for patients who are not candidates for surgery.