Previous History Of Cancer Research Articles

PENTAGON (Predicting Clinical Trials in Gynecologic Oncology): A retrospective study assessing study design factors that affect enrollment in gynecologic cancer trials.

e13647 Background: Obstacles to attaining a diverse clinical trial population contribute to poor representation in medicine, increasing health disparities by limiting generalizability and applicability of findings. Our objective is to evaluate trial enrollment trends according to patient and trial demographics for those who have sought care at our multi-center, mixed-setting Gynecologic Oncology practice. Additionally, we aim to determine specific trial criteria that promote or impede enrollment for patients and physicians. Methods: An IRB-approved, retrospective cohort study evaluating all patients who screened positive for a clinical trial through the Gyn Onc practice’s manual screening process was performed. Screening events were new neoplasms, recurrences or progressions, and changes in treatment. Data was collected from July 2022 to December 2023. Demographic information, trials for which each patient was considered, trials patients enrolled on, and trial characteristics were recorded. Results: After adjustment, there were no significant differences between patient factors (age, marital status, race, ethnicity, and number of screening events) and enrollment status. Of trials available, 9% require biopsy and 94.7% are in person. Most studies are interventional (78.9%) and pharmaceutical trials (73.7%). There was a drastic unadjusted estimated increase in enrollment for Medicaid patients compared to other insurances (55.2% vs 32%, p=.031). There was also an increase in enrollment for cervical cancer patients (18.4%, p=.106) compared to other cancer sites (56.5% vs 32.8%, p=.036). There was a positive relationship between distance traveled to the treatment site and clinical trial enrollment. Patients who lived within 20 miles of the clinical trial site had an enrollment percentage of 30.1% (n=93), compared to 46.55% enrollment for those who lived further (n=58). There was a significant increase in enrollment likelihood without an exclusion criterion of previous history of other cancer (50% vs 33.3%, p=.046). Trials that required no history of chemotherapy had an enrollment of 27.3% (compared to 44.1%). Conclusions: Unlike prior reports, we did not demonstrate differences in trial enrollment by race, socioeconomic or insurance status. This suggests that our objective manual screening process enhances equitable clinical trial offerings. It is possible that this objective manual screening process attenuates provider bias and offers clinical trials to historically marginalized and underrepresented groups.

Atrial fibrillation recurrence in oncocardiological patients treated with catheter ablation. A retrospective cohort study

Abstract Background The relationship between oncological events and cardiovascular pathologies is a subject still widely discussed. Certain chemotherapy drugs, including alkylating agents, anthracyclines, taxanes, and topoisomerase II inhibitors have proven to possess arrhythmic and cardiotoxic capabilities. There is enough evidence to suggest an association between oncological events and the appearance of newly onset AF, but there is little to no scientific literature about the management of these patients and the outcome of normal therapeutically procedures. Purpose This study assess if oncocardiological patients with AF should be considered a risk group when planning to undergo catheter ablation for the arrhythmia treatment. Methods The studied population was based on the data recollection from the electrophysiology department and consisted of patients with AF intervened by radiofrequency catheter ablation. All the procedures were conducted between January 1st 2019 and December 31st 2022. Among 138 participants enrolled for this study, 68 of them had either recent history of oncological events (maximum of 5 years cancer-free). The control group had no previous nor active history of cancer. The cohort with the desired exposure (cancer patients) was compared with a cancer-free group. Two primary outcomes were measured: procedure related complications, and first AF recurrence within the first 12 months. Complications were categorized according to two dichotomous variables: the existence of acute complications directly during the procedure or within the first 12 hours after the end of the procedure, and the occurrence of self-limited arrhythmic events during the blanking period. Results When compared as dichotomous variables (yes/no) with Fisher’s exact test, no statistical significance was observed between the studied cohort and control for complications and events during blanking. The proportion of patients free of sustained episodes of AF at 12 months was 52,9% in the oncologic group and 77,9% in the Control group (P = 0.003; RR of 3.14; 95% CI 1.5 - 6.6) for the oncologic group. When not adjusted by any other factor, association with Cancer was shown (HR 2.43; P =0.005; 95% CI 1.3 – 4.4) for recurrence of arrhythmic events. The regression model with Kaplan-Meier method shows the overall 12-month survival in two groups and the difference between the two survival curves was statistically significant (P=0.0016). Conclusion Oncocardiological patients have demonstrated a significantly higher incidence in post-ablational recurrence when compared with a similar cancer-free control group. Results found in acute and chronic procedural complications were similar in both cohorts.

Abstract PO5-02-14: Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients

Abstract Introduction: The long-term severe adverse events associated with anthracyclines, including irreversible cardiotoxicity, myelodysplastic syndromes, and therapy-related leukemias, led researchers to question the risk-benefit of anthracycline-based chemotherapy regimens, especially for patients without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Docetaxel plus cyclophosphamide (TC) has replaced doxorubicin plus cyclophosphamide (AC) for lower-risk patients that need adjuvant chemotherapy. However, the optimal number of cycles of adjuvant in patients with node-positive or node-negative breast cancer is currently unknown. Methods: We performed a retrospective cohort study of patients with HER2-negative breast cancer, stage I to III, that received adjuvant docetaxel and cyclophosphamide (TC) for four or six cycles, treated from January 2010 to December 2021. Patients were included from four cancer institutions, both private and public, located in the South, Southeast, and Northeast of Brazil. Objectives: To investigate the clinical-pathological characteristics and survival of earlystage HER2-negative breast cancer patients who received four (TC4) or six cycles (TC6) of adjuvant docetaxel and cyclophosphamide (TC). Results: We collected data from six hundred and ninety-eight patients, 98.7% were female with an average age of 52 years, 51.9% were postmenopausal, 14.6% BRCA gene mutation, 66% had some comorbidity, and only 8.4% were not candidates for anthracyclines. Two hundred and twenty-five patients had public and 473 private health insurance. About 13.2% of the patients were hormone receptor negative (HR-) and 86.8% hormone receptor positive (HR+), 57.4% breast-conserving surgery and 77.7% sentinel lymph node (SL). Five hundred sixty-four (80.8%) patients received TC4 and 134 (19.2%) TC6. We observed that patients who received TC 6 had unfavorable prognostic factors such as: (TC4 vs TC6) previous breast cancer (8.7% vs 16.3%) (p=0.002), invasive ductal carcinoma (IDC) (73.4 vs 86.7%) (p=0.009), histological grade 3 (HG3) (34.9 vs 42.9%) (p= 0,085) conservative surgery (59.4% vs 53%) (p=0144), SL (80.9% vs 62.2%) (p =0.001), Lymph node positive (15% vs 42.3%) (p=0.001), pathological stage II (37.5% vs 50%) (p=0.001).Treatment completion rates were 96.5% and 84.3% for TC4 and TC6, respectively (p=0,02). The incidence of grade 3 or higher toxicity with TC6 (14% vs 21.1%; p= 0,043). Febrile neutropenia was observed in 6.7% of both groups. Grade 3 or higher neuropathy was most common with TC6 (2.2% vs 10.3%; p=0,163). Permanent treatment discontinuation was more frequent in the TC6 group (3.4% vs. 9.8%; p=0,004), as well as late toxicity (3.4% vs. 9.2%; p=0,004). Ninety-four percent of the patients completed the proposed cycles of chemotherapy, 72% received adjuvant radiotherapy and 85.4% received adjuvant hormone therapy, with 42% of these receiving an aromatase inhibitor for 5 years. The median follow-up of the entire cohort was 61 months. There was no difference in the 5-year DFS (77.5% vs. 64.7%; p=0.159) or the 5-year OS (89.5% vs. 70.5%; p= 0,06) between patients treated with TC4 and TC6. Conclusion: TC6 was commonly used for patients with unfavorable prognostic factors as history of previous breast cancer, (IDC), HG III, lymph node positive and stage II. Patients who received TC6 had less chance of completing the treatment and more severe toxicity, especially late peripheral neuropathy. There was no difference in DFS or OS. Citation Format: Mila Kraychete, Marcelle Cesca, Guilherme Almeida, Leonardo Santana, Luciana Leite, Solange M. Sanches, Vladmir Cordeiro de Lima, Rafaela Pirolli, Rafael Manea, Felipe Kaneta, Jean Coutinho, Lucas Vian, Waires Zeviani, Marcio Reis, Luciana Landeiro, Clarissa Mathias, Geila Nunez, Tamara Santana, Monique Tavares. Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-14.

Abstract PO2-21-01: Granular Cell Tumors of the Breast: A Case Series

Abstract Objective: Granular cell tumors (GCT) of the breast are rare, Schwann-cell derived tumors that are largely benign in nature, but may present with malignant characteristics in 1-2% of cases. There are few reports highlighting the clinical presentation, cytologic differences, operative management and clinical outcomes of patients with these benign versus malignant GCTs. Here, the authors report the clinical course of 9 patients identified with either benign or malignant GCT of the breast. Methods: The medical records for a total of 9 patients treated for histologically confirmed GCT of the breast between March 2015 and May 2023 at our institution were retrospectively reviewed. Clinical data, imaging findings, immunohistochemical markers, surgical interventions, and clinical follow-up data were collected and analyzed. Results: All patients were female, with a mean age of 46 years (Range: 29-61). 5 (56%) patients presented with left-sided lesions with an average maximum dimension of 1.1 cm (SD: 0.7 cm). All 9 (100%) tumors were positive for S100, 4 (44%) were positive for CD68, and 3 (33%) were positive for Inhibin. 4 (44%) patients underwent local mass excision, 3 (33%) underwent lumpectomy, 1 (11%) underwent lumpectomy with sentinel lymph node biopsy, and 1 (11%) underwent partial mastectomy with sentinel lymph node biopsy. There were no perioperative complications nor complications noted at postoperative follow up visits. 1 patient (11%) had 2 recorded recurrences of GCT after the initial breast mass excision, with each tumor exhibiting different positive immunohistochemical markers. 1 (11%) patient had a previous history of breast cancer at time of GCT diagnosis, and 1 (11%) patient had concurrent breast malignancy with the granular cell tumor being in the lymph node of the same breast. Conclusions: Granular cell tumors of the breast are rare Schwann cell derived tumors that often present near breast scar tissue as spiculated, ill-defined masses with microcalcifications on radiologic imaging, mimicking breast malignancy, leading to overtreatment. This study found that for GCTBs that present in lymph nodes, regardless of low malignant potential seen histologically, there was a higher risk of recurrence, and may require further workup and close follow up after wide local excision. For all other granular cell tumors presenting with normal appearing lymph nodes on imaging, a local mass excision was adequate in management, with low risk of recurrence or malignant potential. Future studies should be performed analyzing long-term follow up for these patients to determine risk of recurrence over longer periods of time, and risk for breast malignancy. Granular Cell Tumor Characteristics Tumor characteristics including laterality, tumor location, maximum dimension in centimeters, and positive immunohistochemistry markers were shown for each patient. Citation Format: Shwetha Kochi, Madeline Karsten, Monika Masanam, Teagan Thorson, Roshanak Derakhshandeh, Patricia Wehner, Lucy De La Cruz, Jennifer Son. Granular Cell Tumors of the Breast: A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-21-01.

Abstract PO1-12-04: Exploring Factors Associated with Sexual Well-being and Breast Satisfaction Among Women with Early-stage Breast Cancer

Abstract BACKGROUND: Breast cancer affects not only physical health but also psychological and emotional well-being. Among the various aspects that impact the quality of life of breast cancer patients, sexual well-being and body image in terms of breast satisfaction play a crucial role. Unfortunately, these aspects are often overlooked and undervalued in healthcare, leading to inadequate care and support for breast cancer patients. This study delved into the factors that influence breast satisfaction and sexual well-being in early-stage breast cancer patients who have recently received a cancer diagnosis. We aim to offer providers a more patient-centered and comprehensive approach to breast cancer care. METHODS: This prospective questionnaire-based study screened 175 early-stage breast cancer patients recently diagnosed at a university-affiliated community hospital in Michigan from October 2022 to June 2023. Participants with a previous history of chemoradiation and advanced-stage breast cancer were excluded. Structured telephone interviews were conducted to obtain informed consent and assess patients' breast satisfaction and sexual well-being. Participants were interviewed after their recent breast cancer diagnosis and before undergoing surgical intervention. A validated BREAST-Q questionnaire was used, and their scores were converted to equivalent Rasch scores for interpretation (0=worst, 100=best). Pre-existing medical conditions, social history, and other variables were collected through electronic medical records review and confirmed by interview. Statistical analyses were performed using SPSS version 28.0, and a p-value less than 0.05 was considered statistically significant. RESULTS: Of 175 patients initially screened, 56 met the selection criteria. 75% (N=42) participated, while 25% (N=14) were excluded as they declined to participate or were unreachable via telephone. 81% were White, 14% were Black, and 5% were Hispanics. The cancer stages of the patients were Stage 0 (29.3%), I (48.8%), II (12.2%), and III (9.8%). The mean breast satisfaction score of participants was 67.1 (N=42), and the mean sexual well-being score was 44.6 (N=36). The study found that only the type of surgery was observed to be significantly related to the breast satisfaction of patients. Interestingly, patients who chose mastectomy had higher breast satisfaction scores (75.6 vs. 62.9, p< 0.05) and were relatively younger (59 years vs. 67 years, p< 0.05) than those undergoing lumpectomy. No other demographic factors (race, education, marital status, BMI), social history (smoking), bra size, or pre-existing medical conditions (hypertension, diabetes) were found to affect breast satisfaction among these patients. On the other hand, age had a negative correlation with sexual well-being (mean age=64 years, p< 0.05), while income had a positive correlation (mean income=$ 76,170 annually, p< 0.05). No other variables were significantly associated with patients’ sexual well-being. CONCLUSION: The study revealed that the patient's sexual well-being was significantly associated with age and income, while breast satisfaction was only related to the type of surgery. These findings underscore the importance of considering multiple aspects of a patient's life when designing a comprehensive treatment plan following a cancer diagnosis. By providing additional support and resources tailored to these specific needs, healthcare providers can enhance patients' overall quality of life and promote greater satisfaction with their treatment outcomes. Citation Format: Kim Abbegail Aldecoa, Yi Lee, Lisa Deptula, Chioma Mbionwu, Ewomamobuho Eto, Esentur Salamatov, Megan Frame, Andrea Briefs Ferris, Geetha Krishnamoorthy, Amy Kirby, Judie Goodman. Exploring Factors Associated with Sexual Well-being and Breast Satisfaction Among Women with Early-stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-04.

A Cautionary Note on Pembrolizumab use in Patients with Ascending Aortic Aneurysms.

We describe a case of a patient treated with pembrolizumab (an immune checkpoint inhibitor) for metastatic scalp melanoma. He had a previous history of colorectal cancer, prostatic cancer and chronic polymyalgia rheumatica. The patient was known to have a stable ascending aortic aneurysm of 4.5 cm. However, he developed a rapid expansion of the ascending aortic aneurysm with the size crossing the threshold for surgery. The patient was referred to the cardiothoracic surgery service for intervention and he subsequently underwent surgery. The patient was electively admitted one week later for resection of aortic aneurysm, aortoplasty and external graft fixation. Pathologically, gross evidence of dissection was not identified; however, the histological analysis of the media showed laminar medial necrosis, multifocal in nature, with occasional clusters of histiocytic cells appreciated at their edge reminiscent of that seen in an inflammatory aortitis (granulomatous/giant cell type). Immune checkpoint inhibitor-induced aortitis is becoming increasingly evident, and its presentation can vary. It has been discovered incidentally on surveillance imaging with the use of nivolumab. In other cases, patients have been symptomatic to severely symptomatic. Atezolizumab with carboplatin and etoposide has been reported to cause abdominal aortitis which was responsive to corticosteroids and subsequent discontinuation of atezolizumab. Pembrolizumab has been linked to a case of transverse aortic arch aortitis. In our case, the inflammatory aortitis due to pembrolizumab was the cause of the rapid expansion of the ascending aortic aneurysm. Patients with known aortic aneurysms should undergo careful surveillance when commencing immune-checkpoint inhibitor therapy. Immune checkpoint inhibitors are being increasingly used in the treatment of metastatic malignancy. However, they are a relatively new group of medications, and the side effect profile of each is yet to be fully recognised. Aortitis has occurred with several different immune checkpoint inhibitors.Patients with known aortic aneurysms should undergo careful surveillance when commencing immune checkpoint inhibitors.All interventional therapeutic options should be considered early in these patients on the development of aneurysmal expansion.

Need for Staging Investigations in Newly Diagnosed Breast Cancer: Establishing Local Guidelines for Radiological Staging in Bahrain

Need for Staging Investigations in Newly Diagnosed Breast Cancer: Establishing Local Guidelines for Radiological Staging in Bahrain

Abstract 2449: Case report: DETECT-A participants with pre-malignant conditions

Abstract Background: Blood based tests for multi-cancer early detection (MCED) are being developed to facilitate the earlier detection of various cancer types. The Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing (DETECT-A) study evaluated the CancerSEEK MCED test, an early version of the Exact Sciences MCED test in development, in 9,911 women, age 65-75, without previous history of cancer (Lennon et al., Science 2020). The degree to which MCED testing will facilitate detection of precancerous conditions or incidental findings is unclear. Here we focus on DETECT-A participants who had pre-cancerous conditions diagnosed during a diagnostic work-up for a positive CancerSEEK MCED test. Methods: In a post-hoc analysis, we report on the detection of precancerous conditions consequent to CancerSEEK MCED testing and follow-up. Electronic health records were reviewed for diagnostic procedures performed, details of premalignant and cancer diagnoses, and vital status. Results: In three individuals, mutations in PIK3CA, TP53, or KRAS genes led to a positive CancerSEEK MCED test result. The prescribed imaging protocol using 2-deoxy-2[fluorine-18] fluoro-D-glucose positron emission tomography-computed tomography (18-FDG PET-CT), revealed a 10.3 × 9.8 × 7.8(cm) ovarian mucinous cystadenoma, a 0.8 cm appendiceal mucinous neoplasm, and 3 colonic polyps displaying high-grade dysplasia. All three participants were diagnosed with clinically significant pre-cancerous lesions, subsequently underwent surgical treatment, and remain alive and cancer-free as of February 2023 (Table 1). Conclusion: The diagnostic evaluation of a positive MCED test may occasionally reveal clinically significant pre-cancerous conditions amenable to interventions. The frequency of such findings and their clinical impact warrants further study. Citation Format: Omair A. Choudhry, Angana Kharge, Seema P. Rego, Paul Z. Elias, Adam H. Buchanan, Anne Marie Lennon, Nickolas Papadopoulos, Frank Diehl, Tomasz M. Beer. Case report: DETECT-A participants with pre-malignant conditions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2449.

A rare case of cutaneous metastasis of bladder transitional cell carcinoma

Introduction: The cutaneous metastasis of bladder transitional cell carcinoma (TCC) is uncommon. The number of publications describing this entity is sparse. The cutaneous metastasis manifestation may occur at the time of diagnosis or appear months to years after the diagnosis of bladder TCC. Case description: A 61-year-old male patient presented with a palpable lump in the right lower back that felt for two months before visiting the urology outpatient clinic for routine postoperative follow-up after radical cystectomy one year before. The patient underwent tumor excision, and the pathological analysis supports the diagnosis of metastatic bladder transitional cell carcinoma. The patient then underwent chemotherapy using the gemcitabine-cisplatin protocol. Two years after the cutaneous lesion was diagnosed, the patient is currently surviving. Conclusion: Cutaneous metastasis of the bladder TCC is a rare disease condition where possible diagnostic difficulties may occur, and a specific treatment protocol is also yet to be defined. In patients with a previous history of bladder cancer with cutaneous lesions, metastatic disease must be considered in the differential diagnosis.

INITIAL HFRT EXPERIENCE ON TREATING LARGE BRAIN METASTASES LESION: A CASE REPORT

Abstract
 Background: Brain metastases in cancer patients are increasing, due to advances in imaging and systemic treatment. Stereotactic Radiosurgery (SRS) is a high-end radiotherapy technique that is preferred to treat small brain metastases. Hypofractionated Radiotherapy (HFRT) is an alternative technique that demand lower requirements and ideal for treating larger brain metastases. This case report intended to report our institution initial experience using HFRT in limited setting to treat a patient with large brain metastases. 
 Case Presentation: A-43 years old women with previous breast cancer history was admitted with general weakness and severe headache since 2 weeks before admission. A CT scan exam shows multiple metastatic lesions on both parietal lobe, the largest lesion measures ≥ 3cm in diameter with a prominent vasogenic edema that caused lateral ventricle compression and mild midline shift.
 Discussion: SRS is preferred to treat brain metastases due to its efficacy and excellent therapeutic ratio. Unfortunately it has limitation in treating large metastatic lesions. For such lesions, HFRT being a simpler radiation technique can be opted to achieve acceptable local control and low toxicities profile. We use HFRT to treat a patient with large brain metastases lesion using IMRT with 10 x 4Gy fractionation scheme. The evaluation results 6 weeks later shows no viable brain lesion without any cognitive deterioration reported.
 Conclusion: HFRT for large brain metastases treatment is safe and viable to conduct in institution with limited resources. This relatively simpler technique compared to SRS should be considered to achieve acceptable therapeutic ratio with minimal toxicities.

BRCA mutations: screening for germ-line founder mutations among early-onset Syrian breast cancer patients

BackgroundBreast cancer (BC) is the most common female cancers in many countries including Syria. Familial breast cancer or previous family cancer history are considered significant risk factors. Therefore, detecting the prevalence and founder mutations in the population facilitates genetic counselling, risk assessment and the development of a cost-effective screening strategy. In this study, we investigated the three germ-line founder mutations in the BRCA1/2 genes: [NM_007294.4 (BRCA1):c.68_69del (p.Glu23fs), NM_007294.4 (BRCA1):c.5266dup (p.Gln1756fs) and NM_000059.4 (BRCA2):c.5946del (p.Ser1982fs)], to examine their incidence and frequency in early-onset breast cancer cases and determine if they are connected to familial breast cancer. One hundred early diagnosed BC females (≤ 40 years old) with no other type of cancer were recruited. Genomic DNA was isolated from peripheral blood samples, and mutations were investigated using the Amplification-Created Restriction Site (ACRS) method.ResultsThe family history of cancer was observed in 61% of the cases, of which 35% were breast cancer; however, none of the screened mutations were detected among BC patients.ConclusionsThe investigated germ-line mutations were not common among Syrian female patients with early-onset BC and were not associated with familial BC. Other mutations in the BRCA1/2 genes or other genes may have a contributing role. Future studies and the need to launch nationwide mutation screening tests for BRCA 1/BRCA2 in the Syrian population are recommended.

Retracted: Effect of Previous Cancer History on Survival of Patients with Different Subtypes of Breast Cancer.

[This retracts the article DOI: 10.1155/2022/6116658.].

Feasibility and diagnostic performance of sentinel node biopsy for staging cN0 oral squamous cell carcinoma in a previously treated neck

AbstractObjectivesStaging of the cN0 neck with sentinel node biopsy (SNB) in early‐stage oral squamous cell carcinoma (OSCC) is validated in patients with a previously untreated neck. We aimed to investigate the feasibility and diagnostic accuracy of SNB and unexpected drainage patterns in patients with cT1‐T2N0 OSCC and a history of previous head and neck cancer comprising treatment of the neck, that is, surgery, radiotherapy, or both.MethodsFifty patients with a previously treated neck diagnosed with a new primary or recurrent cN0 OSCC between 2014 and 2021 were included and retrospectively analyzed. Feasibility was assessed by the rate of successfully performed SNB neck staging procedures. Based on follow‐up data, the diagnostic performance of SNB was evaluated by calculation of negative predictive value (NPV) and false omission rate (FOR).ResultsA SNB staging procedure was successfully performed in 76% (38/50) of the patients. Technical failures were due to the lack of drainage preoperatively or failure in intraoperative SN detection. In patients successfully staged with SNB, the rate of a positive SN was 13% (5/38). In the SNB‐negative group, no patients were diagnosed with a regional node recurrence during follow‐up, and the NPV and FOR were 100% and 0%, respectively. Unexpected lymphatic drainage occurred in 32% (12/38) of the patients.ConclusionSNB is technically feasible in cT1‐2N0 OSCC patients with a previously treated neck with a high diagnostic accuracy. Importantly, SNB enables the detection of individual and unexpected lymphatic drainage patterns.

Characteristics of multifocality/multicentricity in breast cancer and its effect on axillary lymph node metastasis

Multifocal (MF) and multicentric (MC) breast cancers are seen with increasing frequency with advances in imaging methods. However, there is no consensus on the behavior and management of these tumors. In this study, we aimed to investigate the characteristics of MF/MC breast cancers and their relationship with axillary lymph node metastasis (ALNM). Patients who underwent surgery for breast cancer between January 2015 and January 2023 were retrospectively scanned. Exclusion criteria were as follows; male breast cancer, second primary cancer diagnosis, previous breast cancer history, previous excisional/incisional breast biopsy, neoadjuvant chemotherapy, and occult breast cancer. Multiple tumors that were closer than 5 cm to each other were defined as MF, and the others were defined as MC. T stage was determined in two different ways, using the largest tumor diameter (Tmax) and the aggregate tumor diameter (Tsum), and two different multivariate analysis models were applied. A total of 156 patients were enrolled in the study, including 130 unifocal (UF), 17 MF and 9 MC. Lymphovascular invasion (LVI) (p=0.43), ALNM (p=0.23), younger age (<50) (p=0.41) and invasive lobular carcinoma (ILC) (p<0.001) were higher in MF/MC tumors than in UFs. When comparing MF and MC, no difference was seen except progesterone receptor positivity (p=0.017). In both multivariate analyses, LVI and ILC had an effect on ALNM, while no effect of MF/MC was seen. In addition, while T stage had a significant effect on ALNM in the model using Tsum, it did not have a significant effect in the Tmax model. Our retrospective data supports that MF/MC is not a direct risk factor for ALNM and that the main factor affecting ALNM is the total tumor burden.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Endometrioid type adenocarcinoma in situ as a potential precursor lesion for extremely rare invasive endometrioid type adenocarcinoma of the cervix

HPV-independent in situ adenocarcinomas have been only recently added to the WHO 2020 classification. To date, little information has been published about HPVindependent precursor lesions. In particular, regardiong the extremely rare cervical endometrioid type adenocarcinoma thought to arise in the setting of cervical endometriosis, a premalignant lesion is still not well defined. In this short communication we describe a possible precursor to invasive cervical endometrioid type adenocarcinoma in a 39-yr-old patient, with a previous history of breast cancer.

Association between circadian physical activity patterns and cancer incidence through regulation of inflammation: A UK biobank study

BackgroundPhysical activity (PA) has been linked with cancer incidence. However, the effects and mechanisms underpinning circadian PA trajectories on cancer remain elusive. This study aimed to explore the optimal PA patterns in reducing cancer incidence and the associated potential mediators. MethodsBetween 2006 and 2010, 502,400 participants were recruited from the UK Biobank. Out of these, 102,323 participants wore accelerometers, which allowed for collecting acceleration data continuously over 7 days. After excluding participants with previous cancer history, 96,687 participants were included in K-means cluster analysis to identify PA trajectories. The association between PA and cancer incidence was assessed using Cox regression analysis. Additionally, we investigated the mediating role of inflammation. ResultsA total of 5995 cancer cases were recorded during a median follow-up of 7.1 years. Four distinct PA trajectories (persistent low, single peak, double peak, and vigorous) were identified. The ideal PA patterns reduced the risk of 7 out of 17 site-specific cancers, with the lowest hazard ratios and 95% confidence intervals of cancer for bladder (0.59, 0.40–0.86), breast (0.73, 0.60–0.89), kidney (0.45, 0.26–0.78), lung (0.59, 0.41–0.84), myeloma (0.49, 0.27–0.88), and oral & pharynx (0.51, 0.26–0.98) in the vigorous pattern and for colorectal (0.71, 0.54–0.93) in the double peak pattern. Moreover, the mediating effects of inflammation were significant. ConclusionOptimal PA trajectories reduced cancer incidence, especially in double peak and vigorous patterns. The protective effect was associated with both intensity and circadian rhythm. Crucially, this protection was mediated by inflammation regulation.

SARS-CoV-2 Vaccination and the Multi-Hit Hypothesis of Oncogenesis.

Cancer is a complex and dynamic disease. The "hallmarks of cancer" were proposed by Hanahan and Weinberg (2000) as a group of biological competencies that human cells attain as they progress from normalcy to neoplastic transformation. These competencies include self-sufficiency in proliferative signaling, insensitivity to growth-suppressive signals and immune surveillance, the ability to evade cell death, enabling replicative immortality, reprogramming energy metabolism, inducing angiogenesis, and activating tissue invasion and metastasis. Underlying these competencies are genome instability, which expedites their acquisition, and inflammation, which fosters their function(s). Additionally, cancer exhibits another dimension of complexity: a heterogeneous repertoire of infiltrating and resident host cells, secreted factors, and extracellular matrix, known as the tumor microenvironment, that through a dynamic and reciprocal relationship with cancer cells supports immortality, local invasion, and metastatic dissemination. This staggering intricacy calls for caution when advising all people with cancer (or a previous history of cancer) to receive the COVID-19 primary vaccine series plus additional booster doses. Moreover, because these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, safety, and the risk of interactions with anticancer therapies, which could reduce the value and innocuity of either medical treatment. After reviewing the available literature, we are particularly concerned that certain COVID-19 vaccines may generate a pro-tumorigenic milieu (i.e., a specific environment that could lead to neoplastic transformation) that predisposes some (stable) oncologic patients and survivors to cancer progression, recurrence, and/or metastasis. This hypothesis is based on biological plausibility and fulfillment of the multi-hit hypothesis of oncogenesis (i.e., induction of lymphopenia and inflammation, downregulation of angiotensin-converting enzyme 2 (ACE2) expression, activation of oncogenic cascades, sequestration of tumor suppressor proteins, dysregulation of the RNA-G quadruplex-protein binding system, alterationof type I interferon responses, unsilencing of retrotransposable elements, etc.) together with growingevidence and safety reports filed to Vaccine Adverse Effects Report System (VAERS) suggesting that some cancer patients experienced disease exacerbation or recurrence following COVID-19 vaccination. In light of the aboveand because some of these concerns (i.e., alteration of oncogenic pathways, promotion of inflammatory cascades, and dysregulation of the renin-angiotensin system) also apply to cancer patients infected with SARS-CoV-2, we encourage the scientific and medical community to urgently evaluate the impact of both COVID-19 and COVID-19 vaccination on cancer biology and tumor registries, adjusting public health recommendations accordingly.

Mutational Profile and Dynamics of PPM1D-Mutant Clones in the Spectrum of Myeloid Disorders

Introduction Mutations in PPM1D a regulator of DNA damage response, are enriched in patients with clonal hematopoiesis (CH) exposed to cytotoxic treatment or with therapy-related myeloid neoplasm. However, their role in leukemic transformation is unclear. Here, we describe a large cohort of patients with PPM1D mutations from CH to acute myeloid leukemia (AML) to understand the molecular landscape of mutant PPM1D related disease and the longitudinal dynamics of CH under treatment. Methods We included, in a non-sequential cohort, 96 PPM1D mutated patients treated at Gustave Roussy with CH, clonal cytopenia of unknown significance (CCUS), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or AML. A 77 gene panel NGS analysis was performed. An additional 16 PPM1D mutated AML patients from ALFA trials (1200, 0701,0702) were included. 10 patients with ovarian cancer from this cohort had sequential blood samples (OvBIOMark trial) available prior to hematologic evaluation, from the diagnosis or first relapse of their cancer through the course of therapy. Those samples were analyzed with a UMI based 18 gene panel (HaloplexHS, Agilent). Overall survival (OS) analyses were performed with the Kaplan-Meier method from the time of diagnosis until death from any cause. Results Among the 112 patients with PPM1D mutations, 23 (21%) had CH, 36 (32%) CCUS, 19 (17%) MDS, 25 (22%) AML (including 4 relapses), and 9 (8%) MPN. Median age was 65 [range, 21-88] years with 67% of females. Only 18% of the patients had no previous cancer history. Most frequent primary cancers were gynecological cancer (27%), lymphoid malignancies (22%), and breast cancer (17%). Median time between primary cancer diagnosis and hematologic assessment was 5.3 [range, 1.2-8.5] years. Eighty six percent of patients had one PPM1D mutation, 9% had 2, and 5% had 3 or more (restricted to CH and CCUS). Median variant allele frequency (VAF) was 3% [0.2-38], 3% [1-31], 2.4% [1-41], 23% [1-50], and 4% [1-42] in CH, CCUS, MDS, AML and MPN, respectively. Among CH/CCUS patients, PPM1D was the sole detected somatic mutation in 39% (23/59), compared to 9% (5/53) in MDS/AML/MPN patients (odds ratio=6, p=0.0004); 3/5 of the latter had complex karyotype. The most frequently co-mutated genes were DNMT3A (29%) and TP53 (25%), uniformly across all conditions ( Fig 1A). MDS-related gene mutations, RUNX1 (7%), ASXL1 (4%), SF3B1 (4%), SRSF2 (4%), U2AF1 (4%), were specific to AML/MDS/MPN. Among 28 patients with both PPM1D and TP53 mutations, PPM1D mutations were dominant or co-dominant in 64% (18/28), and secondary in 36% (10/28). IPSS-M risk of evaluable MDS was high/very high in 54% (7/13) of patients. ELN 2022 classification of AML was adverse in 68% (17/25) of patients. AML treatment options included best supportive care for 8% of patients (2), 5-Azacytidine for 32% (8), intensive chemotherapy for 60% (15). With a median follow up of 2.4 years, the median OS was 4.6 (CI95%; 4.1-NA), 1.31 (CI95%; 0.53-NA), 1.27 (0.43-NA), 0.66 (CI95%; 0.42-1.26) and 20.4 (CI95%; 20.4-NA) years for CH, CCUS, MDS, AML and MPN, respectively. TP53 mutation status did not stratify OS. Four ovarian cancer patients with CH/CCUS transformed to MDS/AML with a median of 5.3 [1-12] years. At transformation, 3/4 had a stable PPM1D mutation, 1/4 an increase in PPM1D VAF (2 to 28%), and 3/4 had TP53 mutations before and at transformation. We analyzed 67 timepoints from 10 ovarian cancer patients during therapy (median 7 per patient). 10/10 received alkylating agents and 5/10 PARPi. The median number of mutations per patient was 4 and 6 at baseline and last follow-up, respectively. PPM1D-mutated clone size increased from 0.4% [0.1-3] at baseline to 7% [2-30] at last follow-up. Beyond clonal expansion, PPM1D VAF dynamics showed non-linear changes related to alkylating agents exposure: 2/10 patients had a continuous expansion, 2/10 had expansion then contraction (GR-1/3, Fig 1B), and 6/10 had expansion then stabilization (GR-2, Fig 1B). Conclusion We described a large cohort of PPM1D mutated patients from CH to AML. Their prognosis was poor independently of TP53 mutation at AML/MDS stage. PPM1D mutations were frequently part of the dominant clone. To confirm the clonal architecture, single cell sequencing analysis in 8 AML/MDS patients are ongoing. Trajectory of PPM1D mutations in ovarian cancer patients revealed a non-linear alkylating agent dependency which warrants further investigation.

Rare adrenal cavernous hemangioma: a case report highlighting diagnostic challenges.

Adrenal cavernous hemangiomas are rare benign vascular tumors that pose significant diagnostic challenges. Despite their benign nature, features overlapping with malignancies often complicate management decisions. A 64-year-old male presented with a 4.4 cm necrotic left adrenal mass discovered incidentally on imaging. His medical history included papillary thyroid carcinoma, with subsequent thyroidectomy and radioactive iodine ablation. Evaluations for hiccups revealed multiple lung nodules, hypertrophic cardiomyopathy, and anemia. Given the patient's previous cancer history, elevated aldosterone/renin ratio, and mass size, our multidisciplinary tumor board decided to proceed with a left adrenalectomy. Post-surgical pathology confirmed a diagnosis of adrenal cavernous hemangioma. The occurrence of ambiguous adrenal mass with other pathologies, such as our patient's papillary thyroid carcinoma, complicates the diagnostic and therapeutic landscape. As demonstrated in our case, opting for surgery remains a viable solution for adrenal cavernous hemangiomas, especially for masses greater than 4 cm. Interdisciplinary collaboration, exemplified by our tumor board's decision-making process, is crucial for optimal management. This case underscores the need for a multifaceted approach when confronting adrenal masses with such diagnostic ambiguity.