Early-stage Carcinoma Research Articles

Utility of Whole Body 18F-FDG PET/CT in Comparison to Pelvic MRI in Evaluation of Local Staging of Early-Stage Carcinoma Cervix.

This prospective comparative study aimed to investigate the applied value of whole body 2-deoxy-2[fluorine-18]fluoro- D-glucose positron emission tomography integrated with computed tomography (18F-FDG PET/CT) in comparison to pelvic magnetic resonance imaging (MRI) in early cervical cancer patients. A prospective study was performed on 47 clinically early-stage cervical cancer patients evaluated with positron emission tomography/computed tomography (PET/CT) and MRI before surgery. The final postoperative histopathology report served as the reference standard. Both PET/CT and MRI images were analyzed and correlated with histopathologic findings concerning parametrial and lymph node involvement. Sensitivity, specificity, and negative predictive value (NPV) of PET/CT were 33.3%, 81.8%, and 94.7%, respectively, for parametrium assessment. And the corresponding values of pelvic MRI were 33.3%, 63.6%, and 93.3%, respectively (PET/CT versus MRI, p > 0.05). The positive predictive value (PPV) of PET/CT (11.1%) was higher than MRI (5.9%) for parametrial assessment (p < 0.05). The sensitivity, specificity, PPV, and NPV of PET/CT were 75%, 83.7%, 30%, and 97.3%, respectively, for lymph node assessment. And the corresponding values of MRI were 75%, 81.3%, 27.3%, and 97.2%, respectively (PET/CT versus MRI, p > 0.05). There was no significant difference between MRI and PET/CT concerning stage migration (p= 0.4276). The PET/CT had no additional utility (compared to MRI) in the evaluation of local staging of clinically early cervical carcinoma patients.

Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures

To investigate similarities in the gene profile of Oral Lichen Planus and Oral Squamous Cell Carcinoma that may justify a carcinogenic potential, we analyzed the gene expression signatures of Oral Lichen Planus and Oral Squamous Cell Carcinoma in early and advanced stages. Based on gene expression data from public databases, we used a bioinformatics approach to compare expression profiles, estimate immune infiltrate composition, identify differentially and co-expressed genes, and propose putative therapeutic targets and associated drugs. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between Oral Lichen Planus and early and advanced Oral Squamous Cell Carcinoma, with the cornified envelope formation and antigen processing cross-presentation pathways in common between Oral Lichen Planus and early Oral Squamous Cell Carcinoma. Together, these results reveal that key tumor suppressors and oncogenes such as PI3, SPRR1B and KRT17, as well as genes associated with different immune processes such as CXCL13, HIF1A and IL1B are dysregulated in OLP.

Comparison of Surgical Resection and Percutaneous Ultrasonographic Guided Radiofrequency Ablation for Initial Recurrence of Hepatocellular Carcinoma in Early Stage following Curative Treatment.

The SURF trial showed that surgical resection (SR) and percutaneous ultrasonographic guided radiofrequency ablation (RFA) had equal therapeutic effects for small hepatocellular carcinoma (HCC). However, consensus regarding which treatment is appropriate for initial recurrent early-stage HCC remains lacking. This study aimed to elucidate therapeutic efficacy differences between SR and RFA for initial recurrent early-stage HCC. From 2000 to 2021, 371 patients with recurrent early-stage HCC (≤3 cm, ≤3 nodules) after undergoing initial curative treatment with SR or RFA were enrolled (median age 72 years; males 269; Child-Pugh A:B, n = 328:43; SR:RFA, n = 36:335). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated. Although the median albumin-bilirubin (ALBI) score was better in the SR than the RFA group (-2.90 vs. -2.50, p &lt; 0.01), there were no significant differences between them in regard to RFS (median 28.1 months, 95% CI 23.4-50.0 vs. 22.1 months, 95% CI 19.3-26.2; p = 0.34), OS (78.9 months, 95% CI 49.3-not applicable vs. 71.2 months 95% CI, 61.8-84.7; p = 0.337), or complications (8.3% vs. 9.3%; p = 1.0). In sub-analysis for RFS and OS according to ALBI grade revealed no significant differences between the SR and RFA groups (ALBI 1/2 = 28.2/17.5 vs. 24.0/23.4 months; p = 0.881/0684 and ALBI 1/2 = 78.9/58.9 vs. 115.3/52.6 months, p = 0.651/0.578, respectively). This retrospective study found no significant differences in regard to RFS or OS between patients in the SR and the RFA groups for initial recurrence of early-stage HCC after undergoing curative treatment. These results showing equal therapeutic efficacy of SR and RFA confirm the findings of the SURF trial.

Determination of the Optimal Time for Planning Single-Entry Expandable Catheter Brachytherapy for APBI

<h3>Purpose/Objective(s)</h3> APBI treats early-stage carcinoma in women using HDR with a single-entry catheter device with multiple peripheral struts inserted into the cavity post-lumpectomy. A planning CT (CT_plan) is conducted on the day of device implantation (Day 0) or the day after (Day 1). For an asymmetrical implantation, a change in distance between two struts may be seen from day to day, making the device unstable, with no consensus on when struts stabilize in patients. In this retrospective cohort study, the endpoint is the number of days between device implantation and CT_plan to achieve stability. <h3>Materials/Methods</h3> With IRB approval, we retrospectively reviewed 242 women treated with ABPI using HDR from 2014–2021. Daily CT images were reviewed in 34 patients who had qualitative strut instability and asymmetry. Instability was evaluated by superimposing the CT taken each morning to the CT_plan on the Brachytherapy Planning Software (BPS). CT data were exported to BPS, where the percent change of distance between each strut was calculated and compared to the previous day (Days 0–1, Days 1–2, etc.). The average percent change and Standard Deviation (SD) for all distances for each calendar day were determined. Struts were considered unstable if the average percent change from the previous day was greater than 5%. The information biases inherent in retrospective reviews were accounted for by ensuring no missing data. <h3>Results</h3> Strut stability, in terms of the average percent change in all strut-to-strut distances across all patients, occurs on Day 1 (24 hours after device implantation), significantly dropping from 18% (SD = 27%) to 3.6% (SD = 2.8%). Stability remained on subsequent days (Day 1 and beyond), ranging between 2–5% (Table 1). <h3>Conclusion</h3> An increase in days only results in greater strut stability after 24 hours (Days 0–1), demonstrating that waiting for more than 24 hours after device implantation to complete a CT may not be necessary for those with asymmetric and unstable struts. The implication is that this finding can aid in improving treatment efficiency and decreasing infection risk as less time is needed for the device to be inside the cavity to wait for strut stability.

Intraoral Ultrasound in Early Stage Tongue Carcinoma.

Preoperative assessment of depth of invasion (DOI) is critical in the surgical management of early stage carcinoma tongue. Intraoral ultrasound (IOUS) has been recently described as a cost-effective alternative to MRI in the accurate measurement of DOI. We describe the technique of IOUS in different types of lesions (surface, ulcerative, and exophytic); and provide key imaging pearls for the routine use of this novel ultrasound application.

Sonographic features differentiating early-stage ovarian clear cell carcinoma from endometrioma with atypical features

BackgroundOvarian clear cell carcinoma (OCCC) is the most common endometriosis-associated ovarian cancer. Ovarian endometriosis may present with atypical or malignant sonographic features and interfere with clinical judgment about whether definitive surgical intervention is required.ObjectiveTo compare the characteristics of endometrioma with atypical features and OCCC.MethodsThis study enrolled patients with pathologic diagnoses of either endometrioma or OCCC. For patients with endometrioma, only those with atypical features, defined as the presence of at least one of the following sonographic characteristics: cyst diameter of 10 ± 1 cm, multi-cystic lesions, any solid component or papillary structure, and blood flow of any degree, were included.ResultsSixty-three patients had endometriomas with atypical features, while 57 patients had OCCC. Patients with endometriomas were younger (39.33 ± 7.04 years vs. 53.11 ± 9.28 years, P < 0.01), had smaller cysts (7.81 ± 2.81 cm vs. 12.68 ± 4.60 cm, P < 0.01), and had smaller solid components (0.93 ± 1.74 cm vs. 4.82 ± 3.53 cm, P < 0.01). In contrast, OCCCs were associated with loss of ground-glass echogenicity (6.3% vs 68.4%, P < 0.01). In multivariate analysis, advanced age (> 47.5 years), large cysts (> 11.55 cm), large solid components (size > 1.37 cm), and loss of ground-glass echogenicity were independent factors suggestive of malignancy.ConclusionAdvanced age, larger cyst sizes, larger solid component sizes, and loss of ground-glass echogenicity are major factors differentiating endometriomas from malignancies. For women in menopausal transition who have finished childbearing who present with endometrioma with atypical features, removal of the adnexa intact could be considered.

Endoscopic management of tumors of minor ampulla: a multicenter study.

Background and study aims Papillary and duodenal carcinoma are aggressive cancers with poor 5-year survival rates. Papillectomy is a well-established treatment for early-stage carcinoma of the major papilla. Tumors arising in the minor papilla are relatively rare and there is little research available on the endoscopic management of these tumors. Patients and methods The purpose of this study was to establish the safety and efficacy of endoscopic papillectomy in the management of minor papillary tumors. A total of six patients undergoing ERCP for papillectomy for minor papillary tumor at four hospitals were included in this study over a period of 5 years. Results Papillectomy was technically successful in all six patients. Pathology revealed adenoma in three patients, adenoma with high-grade dysplasia in one patient, carcinoma in one patient, and carcinoid tumor in one patient. For follow-up, one patient had an additional tumor identified at 2 years which was found to be a recurrence of the original adenoma. This patient was treated with repeat papillectomy with no further evidence of recurrence. Conclusions In our pilot study, we demonstrate that endoscopic papillectomy appears safe and effective in the management of minor papillary tumors.

Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study.

PurposeTo assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively.MethodsWe studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC.ResultsIn TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively.ConclusionsFor TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.

Two year results of blessed: Expanded access for deltarex-g for an intermediate size population with advanced pancreatic cancer and sarcoma (NCT04091295) and individual use IND for EARLY-STAGE invasive carcinoma of breast (IND# 19130) .

e15048 Background: Defects in cell cycle control are fundamental oncogenic drivers and targeting deregulated cell cycling is under intensive study. Cell cycle cyclin G1 (CCNG1) inhibitor therapy, exemplified by DeltaRex-G, a tumor-targeted retro vector encoding a cytocidal CCNG1 inhibitor gene, has been tested in over 280 cancer patients worldwide in early studies, inducing long term (10-13 years) survival in certain patients with intractable metastatic pancreatic adenocarcinoma, sarcoma, and breast cancer. Hence, further clinical development of DeltaRex-G for cancer patients who have few or no therapeutic options is apropos. Methods: Primary objective: To determine overall survival. Secondary objective: To evaluate disease control, best overall response, and incidence of treatment-related adverse events. Patient and Methods: Study 1 is entitled “Blessed: Expanded Access for DeltaRex-G for Advanced Pancreatic Cancer and Sarcoma (NCT04091295)”. Study 2 is entitled “Compassionate Use of DeltaRex-G for Advanced Cancers. In both studies, patients will receive DeltaRex-G at 1-3 x 10e11 cfu i.v. over 15-30 minutes, 3 x a week until significant disease progression or unacceptable toxicity occurs. Results: Seventeen patients were enrolled, 9 sarcomas, 2 pancreatic adenocarcinomas, 1 non-small cell lung cancer, 2 breast carcinoma, 1 prostate cancer, 1 cholangiocarcinoma, and 1 basal cell carcinoma and actinic keratosis. Three patients were enrolled in Study 1 and 14 patients were enrolled in Study 2. Two patients were initially enrolled in Study 1 and later enrolled in Study 2. Twelve of 17 enrolled patients were treated with DeltaRex-G monotherapy or in combination with FDA-approved cancer therapies. Of the 12 treated patients, 5 are alive 10 to 30 months from DeltaRex-G treatment initiation. Two patients with early-stage triple receptor-positive and triple receptor-negative breast cancer who received DeltaRex-G as adjuvant/first-line therapy are alive one year in complete remission; 2 patients with chemo-resistant Stage 4 sarcoma are alive 2 1/2 years, and one patient with advanced basal cell carcinoma is alive 10 months from treatment initiation. There were no treatment-related adverse events reported. Conclusions: Taken together,the data suggest that (1) Adjuvant/first-line therapy with DeltaRex-G may reduce the incidence of recurrence of early-stage invasive carcinoma of the breast and (2) DeltaRex-G may evoke tumor growth stabilization after failing standard chemotherapy. Phase 2 studies are planned to evaluate if DeltaRex-G (1) will reduce the incidence of recurrence in early-stage invasive carcinoma of breast, (2) improve survival in pancreatic cancer, and (3) prolong progression-free survival and overall survival in advanced sarcoma. Clinical trial information: NCT04091295.

Risk of contralateral breast and other cancers in patients with invasive lobular breast cancer.

555 Background: Women with early-stage breast cancer (BCa) are living longer, and survivorship issues including second primary cancers (SPCs) are therefore increasingly important. This study seeks to determine the risk of SPCs, including contralateral breast cancer (CBCa), in women with early-stage invasive lobular carcinoma (ILC). Methods: The study population consisted of women with BCa diagnosis between 2000-2018 within the NCI Surveillance, Epidemiology, and End Results (SEER v 3.2.9) registry and between 2000-2021 in the Mayo Clinic Cancer Registry. In the SEER registry, the standardized incidence ratios (SIR) for SPCs were estimated for adult women with histologically confirmed early stage (I-III) ILC compared to the development of any primary cancer in the general population. For reference, SIRs for SPCs for a similar patient population with invasive ductal carcinoma (IDC) of the breast were also estimated. For comparison of CBCa between ILC and IDC, follow up records from the Mayo Clinic Cancer Registry were evaluated among adult women who underwent lumpectomy or unilateral mastectomy for early stage ILC or IDC. A multivariable Cox proportional hazards regression was performed to compare the risk of CBCa between ILC and IDC while adjusting for the age at diagnosis, race/ethnicity and estrogen receptor status of the primary tumor. Results: An increased incidence (p&lt;0.05) of any SPCs and second BCa was noted for both ILC and IDC compared to the expected rate of primary cancer in the general population (Table). Interestingly, women with ILC were observed to have a significantly increased incidence of subsequent gastric cancer which was not seen for women with IDC. An SIR &gt;1.5 was noted for subsequent risk of sarcoma, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) for both ILC and IDC (Table). In the Mayo Clinic Cancer Registry of 2,218 women with ILC and 14,629 women with IDC meeting the inclusion criteria, the 5-year risk of CBCa was 2.6% and 1.5% (log rank statistic p-value =0.001) for ILC and IDC respectively. A significantly increased risk of CBCa was noted in women with ILC (Hazard Ratio 1.82, 95% CI 1.34-2.47, p&lt;0.001) compared to women with IDC in the multivariable analysis. Conclusions: Women with ILC may have an increased risk of SPC and second BCa compared to the risk of any primary cancer in the general population. The increased incidence of gastric cancer and the higher risk of CBCa in ILC survivors compared to women with IDC is intriguing and needs to be investigated further including evaluation of the role of germline genetic factors. [Table: see text]

A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible muscle invasive bladder cancer (RAD VACCINE MIBC).

TPS4611 Background: The utilization of neoadjuvant immune checkpoint inhibitor (ICI) therapy, including anti-PD1/L1 agents, prior to radical cystectomy (RC), is an emerging paradigm in muscle invasive bladder cancer (MIBC). Pathologic complete responses (pCR) have been observed in 25-40% of patients with neoadjuvant PD1/L1 inhibitor monotherapy for cisplatin-ineligible MIBC. In situ vaccination using stereotactic body radiation therapy (SBRT) may augment T-cell responses to tumor-specific antigens through immunogenic cell death. Sasanlimab (PF-06801591) is a humanized IgG monoclonal antibody that targets PD-1 selectively, for which there are both Phase 1 data and ongoing Phase 3 trials in early-stage urothelial carcinoma. There exists a strong rationale to evaluate a novel strategy of combination neoadjuvant ICI therapy with SBRT as an in situ vaccine to improve loco-regional control and decrease the risk of distant recurrence in cisplatin-ineligible patients with MIBC. Methods: This is a prospective, investigator-initiated, single-arm, single-institution, phase II trial that evaluates neoadjuvant sasanlimab in combination with SBRT as neoadjuvant therapy for patients with MIBC before RC. Eligibility requires patients to be cisplatin-ineligible (one of the following: ECOG-PS=2, creatinine clearance &lt;60 ml/min, or comorbidities such as hearing loss or neuropathy) or those who refuse cisplatin-based chemotherapy. Sasanlimab (300 mg) will be administered subcutaneously on Day 1 of each 28-day cycle for a total of 2 cycles, in combination with SBRT to the primary tumor at a dose of 24Gy given in 3 fractions, starting on Day 1 of Cycle 2 with a 48-hour interval between fractions. The combination treatment will be assessed by using a Simon’s 2-Stage design, which the first 10 patients are enrolled as a safety lead-in to evaluate the safety and feasibility. Futility analysis will be performed after a total of 18 patients. The primary endpoint is pCR rate after neoadjuvant sasanlimab/SBRT, followed by RC. If pCR is observed in 4 or fewer patients, further enrollment of patients may be stopped with the conclusion that pT0 cannot be 40% or greater. Otherwise, an additional 15 patients will be accrued in stage II, resulting in a total of 33 patients. Secondary endpoints include adverse events, surgical complication rates, health related quality-of-life, overall survival, and recurrence free survival. Exploratory endpoints include analysis of and association with pCR of the tumor/germline genetic signatures, circulating tumor DNA, tumor PD-L1 expression, blood cytometry time-of-flight analysis to identify immune response. Enrollment opened on February 15, 2022. Clinical trial information: NCT05241340.

Disease-free and overall survival outcomes for localized RCC patients by disease stage.

e16526 Background: Real world evidence (RWE) on patient outcomes among early-stage non-metastatic renal cell carcinoma (RCC) patients (pts) of different risk groups are limited. This RWE study evaluated disease free survival (DFS) and overall survival (OS) patterns and risk of OS among pts with non-metastatic RCC in the US. Methods: This retrospective analysis identified pts, age ≥18 years, with non-metastatic RCC diagnosis between 01/01/2012-12/31/2015, and surgical treatment for RCC prior to metastatic diagnosis. Pts were identified from the ConcertAI Oncology Dataset which draws electronic medical records from 100 community oncology clinics in the US and followed until 08/19/2021. Pts were stratified into intermediate (int)-high (pT2N0 high grade, pT3N0) or high risk (pT4N0, pTanyN1) RCC. Time to event outcomes (DFS, OS) were examined using Kaplan-Meier methods, and association of recurrence and 5yr OS was examined using Cox proportional hazard model, controlling for baseline and clinical characteristics. DFS was defined as time from initial nephrectomy to first recurrence or death, whichever occurred first. OS was defined as time from initial nephrectomy to death. Results: The study included 274 pts (87% int-high risk, N = 239; 13% high risk, N = 35). Overall, pts were 63.5 yrs (median age), 66% male, 78% White, and 73% had clear cell RCC. Median follow-up was 49.5 months (mths). 54% int-high and 69% high risk pts had recurrence. As seen in the table, median DFS ranged from 14.6-64.8 mths and 5yr DFS rates ranged from 10-61% across risk groups. Median OS was 83.4 mths for int-high and 78.4 mths for high risk pts; 5yr OS rate was 69% for int-high and 58% for high risk. Compared to patients without recurrence, pts with recurrence had shorter median OS (93.8 vs 69.6 mths) and lower 5yr OS rate (85% vs 57%). In pts with recurrence, 5yr OS rate was similar between int-high and high risk groups (58% and 57%). Pts with recurrence were 2.4 times (HR = 2.4; 95% CI = 1.5, 3.9) more likely to die 5 yrs post initial nephrectomy compared to pts without recurrence. Conclusions: This study confirms findings from our previous research with SEER data that pts with recurrence had an increased risk of death, compared to pts without. The DFS and OS rates observed in this RWE study are supportive of DFS and OS rates observed in the placebo arm of the KEYNOTE-564 trial. Additionally, poor DFS rates were observed within subgroups of int-high risk pts. The study results indicate the high real-world unmet need in post-nephrectomy int-high or high risk localized RCC pts, highlight the need for effective adjuvant treatments, and inform the design of future interventional trials in non-metastatic RCC pts.[Table: see text]

Melatonin supplementation for preventing cancer-related fatigue in patients receiving radiotherapy for early-stage breast cancer: A double-blind placebo-controlled phase III trial.

e24079 Background: Fatigue is common in patients undergoing radiotherapy (RT). Melatonin, an inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The effect of melatonin for prevention of fatigue and other symptoms was evaluated in a double-blind placebo-controlled trial. Methods: Early-stage or ductal carcinoma in-situ breast cancer patients ≥ 18 years, female, Eastern Cooperative Oncology Group performance status (ECOG PS) &lt; 3, hemoglobin ≥9 g/dL. RT with curative intent, randomized 1:1 to melatonin 20 mg or oral placebo, starting night before RT initiation until 2 weeks post-RT. Sample size of 142 evaluable patients in each arm for 80% power and interim analysis at mid recruitment using the unified family method rho = 0.3. Randomization stratified to RT duration (&lt; 3 weeks, ≥3 weeks) and prior chemotherapy. Primary outcome : Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale after completion of RT with additional scores measured at baseline, 2 and 8 weeks post-RT. Secondary outcomes : FACIT-F subscales, Edmonton Symptom Assessment System (ESAS) and Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a. Secondary analyses reported using an F-test at a 5% significance level. Results: For this interim analysis, 85 patients screened; 80 randomized; 39 received melatonin and 38 placebo. 72 included in the analysis as 5 patients had no post baseline FACIT score. Characteristics of age, race, and ECOG PS similar in both arms. Treatment X time for FACIT-Fatigue not significant for melatonin compared to placebo (p .83). FACIT physical, emotional, and functional well-being scores not significantly different (p .35, .62, and .71) but showing a trend for social well-being (p .06). PROMIS scores not changed over time (p .34). ESAS individual symptoms of anxiety, well-being, drowsiness, poor appetite, nausea, pain, shortness of breath, sleep and tiredness not significant, except for depression (p.04). However, a decrease of 0.01 unit in depression score is not considered clinically significant. No grade 3 or 4 adverse events. No participants died during study, 2 died after study completion from breast cancer recurrence. 16 withdrew prior to study completion because of adverse events, unrelated hospitalizations, RT discontinuation, and COVID-19 precautions. Trial was stopped based on statistical analysis demonstrating no difference for primary outcome and imminent expiry of available drug. Discontinuation was approved by Data Safety Monitoring Committee. Conclusions: Melatonin did not prevent fatigue in patients with early stage breast cancer undergoing RT. Melatonin also demonstrated no benefit for other symptoms, except depression. Analysis showed little evidence of an effect, and the trial was terminated early. Clinical trial information: NCT02332928.

49P Analysis of HER2-low carcinomas and PAM50 signature in an early-stage breast cancer cohort

HER2-low (IHQ score 1+ or 2+ with negative in situ hybridization) has emerged as a new potential biomarker in metastatic breast cancer. However, its prognostic value in early-stage carcinomas needs to be revisited. We aimed to evaluate the association of HER2-low carcinomas with PAM50 risk groups combined with standard clinicopathological variables in early breast cancer.

Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study

We present a multiscale agent-based model of ductal carcinoma in situ (DCIS) to study how key phenotypic and signaling pathways are involved in the early stages of disease progression. The model includes a phenotypic hierarchy, and key endocrine and paracrine signaling pathways, and simulates cancer ductal growth in a 3D lattice-free domain. In particular, by considering stochastic cell dedifferentiation plasticity, the model allows for study of how dedifferentiation to a more stem-like phenotype plays key roles in the maintenance of cancer stem cell populations and disease progression. Through extensive parameter perturbation studies, we have quantified and ranked how DCIS is sensitive to perturbations in several key mechanisms that are instrumental to early disease development. Our studies reveal that long-term maintenance of multipotent stem-like cell niches within the tumor are dependent on cell dedifferentiation plasticity, and that disease progression will become arrested due to dilution of the multipotent stem-like population in the absence of dedifferentiation. We have identified dedifferentiation rates necessary to maintain biologically relevant multipotent cell populations, and also explored quantitative relationships between dedifferentiation rates and disease progression rates, which may potentially help to optimize the efficacy of emerging anti-cancer stem cell therapeutics.

Clinicopathological characteristics and treatment outcomes of occult breast cancer: a population-based study

BackgroundOccult breast cancer (OBC) is a special type of breast cancer. Because of its rarity, clinicopathological information is still insufficient, causing a controversial condition about its treatment recommendation. Thus, we aimed to clarify major clinicopathological information, treatment strategies and prognosis of OBC based on a large population.MethodsWe retrospectively collected adult female OBC population from Surveillance, Epidemiology, and End Results database. We divided the whole cohort into two groups based on surgical treatment in-breast. Descriptive analysis of 18 clinicopathological variables was conducted. Survival analysis was performed based on different clinicopathological factors. Univariate and multivariate Cox regression analysis was performed to identify potential independent predictor for prognosis of OBC.Results1189 OBC patients were in final analysis and most of them were diagnosed as an early-stage carcinoma. Patients received breast-conserving treatment (BCT) was nearly two times of ones received mastectomy. Patients receiving radiotherapy in BCT group were significantly more than patients receiving radiotherapy in mastectomy group (61.76 vs. 50.9%, P < 0.001). After a median follow-up period of 62 months, 5-year and 10-year overall survival (OS) of all subjects was 81.6% and 68.8%, respectively. No significant difference in OS and breast-cancer specific survival (BCSS) was found between mastectomy and local breast-conserving surgery. Older age and larger number of positive lymph nodes causes a worse prognosis whereas radiotherapy brought a better clinical outcome for OBC patients.ConclusionsOBC has a generally good prognosis. Less-intensive surgery does not negatively impact clinical outcomes of OBC while additional radiotherapy is totally beneficial to prolong OS and BCSS.

Brachytherapy for primary nasal vestibule cancer using Au-198 grains

Radiation therapy (RT) is one of the definitive treatments for early-stage nasal vestibular carcinoma and has similar local control rates to resection surgery. There are various methods, including external beam RT and brachytherapy. This report describes a case who showed local control for more than 5 years after brachytherapy alone using Au-198 grains for nasal vestibular carcinoma. A 68-year-old Japanese man complained of swelling and pain in his left nasal cavity. He was diagnosed with squamous cell carcinoma (SCC) (cT1N0M0, stage I). An elevated mass of 8 mm in long diameter was found inside the left nasal cavity. Since the patient selected brachytherapy, nine Au-198 grains 185 mBq were permanently injected percutaneously under local anesthesia, and 85 Gy was prescribed. Grade three dermatitis was observed as an acute adverse event. After 2 years, mild telangiectasia of the left nasal skin and epilation of nasal hair in the left nasal cavity was regarded as late adverse events. The patient continues to keep a complete response for 5 years. For small nasal vestibular SCC, brachytherapy with Au-198 grains might be a good option.

Systematic Lymphadenectomy and Oncological Outcomes of Women With Apparent Early-Stage Clear Cell Carcinoma of the Endometrium: A Multi-Institutional Cohort Study

ObjectiveThe survival value of systematic lymphadenectomy for endometrial cancer is ambiguous and controversial. The current study aimed to evaluate the long-term survival role of combined pelvic and para-aortic lymphadenectomy in patients with presumed early-stage clear cell carcinoma of the endometrium.MethodsPatients in three Chinese teaching hospitals who presented between 2012 and 2017 with apparent early-stage clear cell carcinoma of the endometrium and underwent surgical staging were selected. Patients who did and did not undergo systematic lymphadenectomy were identified and clinicopathological characteristics were compared. Disease-free survival and overall survival were evaluated following the generation of the Kaplan-Meier curves and the comparison using the log-rank test. A Cox proportional hazards model was employed to control for confounders.ResultsA total of 244 patients underwent systematic lymphadenectomy and 89 did not receive lymph node dissection. The demographic and baseline data were comparable between the two groups. The rate of disease-free survival at 5 years was 64.10% in patients who underwent systematic lymphadenectomy and 45.05% in patients who did not undergo lymphadenectomy. Patients who underwent systematic lymphadenectomy had better disease-free survival than those who did not receive lymphadenectomy (HR, 0.54. 95% CI, 0.38-0.76. P=0.000). The rate of 5-year overall survival was 68.87% in the lymphadenectomy group and 53.33% in patients who did not undergo systematic lymphadenectomy. Systematic lymphadenectomy was also associated with improved 5-year overall survival for women with presumed early-stage clear cell carcinoma of the endometrium (HR, 0.58. 95% CI, 0.39-0.85. P=0.005). After adjusting for confounders, systematic lymphadenectomy was still independently associated with improved disease-free survival and overall survival.ConclusionPatients with apparent early-stage clear cell carcinoma of the endometrium who underwent systematic lymphadenectomy had better long-term survival than those who did not undergo systematic lymphadenectomy.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis

ObjectiveIn young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival.MethodsBetween 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts.ResultsDuring 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}.ConclusionsEven after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Short- and long-term recurrence of early-stage invasive ductal carcinoma in middle-aged and old women with different treatments

Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36–2.66] vs. 2.07 [95% CI 0.97–4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26–0.35] vs. 0.43 [95% CI 0.30–0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.