Disease-free Interval Research Articles

Blood glucose monitoring during surgery in dogs to assess completeness of surgical resection of insulinoma: 11 cases.

To evaluate whether intraoperative detection of rising levels of blood glucose could improve the completeness of resection of insulin-secreting tumor tissue and whether this improves long-term outcomes. 11 client-owned dogs diagnosed with insulinoma. Retrospective review of medical records of dogs undergoing partial pancreatectomy as treatment for insulinoma. A blood glucose reading was obtained at induction, following removal of the pancreatic mass and/or after each suspected metastatic lesion until blood glucose had normalized. Disease-free interval and survival time were measures of outcome. A positive increase in blood glucose was detected in all cases, with a mean rise of 6.35 ± 4.5 mmol/L. Mean follow-up was 611 days, mean disease-free interval was 382 days, and median survival time was 762 days. Tumor stage was not associated with outcome. Three cases underwent a second surgery (metastasectomy), achieving further prolongation of disease-free survival. A sustained increase in intraoperative blood glucose provided the surgeon with confidence of more complete resection of insulinoma tissue and resulted in improved outcomes in all cases included in this study. Subsequent metastasectomy of recurrent insulinoma lesions also provided good outcomes. Intraoperative monitoring of blood glucose during surgical treatment of insulinoma resulted in the surgeon continuing to explore and resect abnormal tissue until an increase of glycemia was observed. This was shown to provide the surgeon with more confidence of resection of all active insulinoma tissue and improved clinical outcomes.

The Contemporary Presentation and Diagnosis of Endometrial Cancer Recurrence: When, Where, and How?

ABSTRACT Endometrial cancer (EC) is the most common gynecologic cancer in the United States. Despite a favorable prognosis in many, EC is one of the few cancers with rising mortality rates. This is in part due to recurrence rates, being as high as 50% in patients at high risk. Survival differences between locoregional and distant disease recurrence have prompted increased focus on multimodality adjuvant treatment. Disease surveillance using routine imaging for early detection of recurrence has not shown a survival benefit in those at low risk, and a more accurate profile of recurrence pattern and presentation may aid the screening current infrastructure. This retrospective review aimed to examine patterns of recurrence, presentation, and method of diagnosis of recurrent EC in a large contemporary cohort from a single, high-volume institution. Patients who underwent surgery for an EC diagnosis between June 2014 and December 2020 at Ohio State University Comprehensive Cancer Center were included. Disease recurrence was defined as evidence of disease after a 3-month disease-free interval following primary treatment. In the setting of metastatic disease, only those with a complete radiographic response after adjuvant therapy were eligible for recurrence. Locoregional recurrence was confined to the vaginal vault or pelvis. Multiple logistic regression analysis was used to assess the impact of covariates on the likelihood of receipt of treatment for recurrent disease, overall survival, and time from recurrence to death. A total of 1723 patients were included in the study cohort with a median follow-up time of 2.3 years. A total of 201 participants (11.6%) were included in the recurrence analysis. Of these patients, 120 (59.7%) were symptomatic, with abdominal and pelvic pain being the most common symptoms. Among asymptomatic recurrence cases, 15.4% were diagnosed by imaging at provider discretion, 13.4% were diagnosed by pelvic examination, and 7.5% were diagnosed by CA-125 at provider discretion. Patients diagnosed by pelvic examination were more likely to be at an early stage (66.7% vs 34.5%; P = 0.001), of endometrioid histology (66.7% vs 36.8%; P = 0.003), and without prior adjuvant therapy (48.2% vs 17.9%; P = 0.001). Patients who received adjuvant therapy experienced significantly more locoregional recurrences (60.5% vs 19.7%; P ≤ 0.001), but there was no difference in the median time to recurrence of 12.7 months. Patients with asymptomatic recurrence were more likely to be able to receive treatment than those with symptomatic presentations (91.3% vs 76.7%; P = 0.005). Age at initial diagnosis was associated with receipt of treatment for recurrence. Patients with symptomatic recurrence had a significantly shorter median time from recurrence to death (6.5 vs 11.1 months; P = 0.0053) than asymptomatic patients; however, this was driven by receipt of treatment. Overall survival did not differ significantly between mode of presentation or method of diagnosis. The results of this study find that recurrence for EC was observed in 12% of women, the majority of whom experienced symptoms, and symptomatic patients were less likely to receive treatment, which contributed to a shorter time from recurrence to death. These findings in the context of an increasing mortality for EC suggest improvements in providing timely treatment for recurrent disease are essential.

Risk-adjusted hazard analysis of survival after pulmonary metastasectomy for uterine malignancies in 319 cases

ObjectiveThere is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. MethodsThe database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. ResultsA total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. ConclusionsThe survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

Preoperative Plasma miRNA Levels Predict Prognosis in Early-stage Malignant Melanoma.

Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.

A Model to Predict Treatment Failure in Patients Undergoing Upfront Surgery for Resectable Colorectal Liver Metastases.

Patients who recur in the first year after resection of colorectal liver metastases (CRLM) do poorly. The aim of our study was to predict treatment failure in patients undergoing upfront resection with a nomogram. Data from patients resected between 1991 and 2019 were randomly split (70:30) into two cohorts. Treatment failure was defined as any recurrence or death within 12 months. A nomogram was constructed using multivariable logistic regression on the training cohort and validated using the testing cohort. Overall, 783 patients were included. Primary tumor characteristics included 50% left-sided: 75.2% T3/4 and 56.5% node-positive. The median disease-free interval was 10 months, median number of metastases was 1 (1-50), and with a median size of 3.6 cm (0.2-22); 222 (28.3%) patients recurred within 1 year. Recurrence was mostly extrahepatic with or without liver involvement (150/222, 67.6%). Curative-intent treatment was possible in 37.8% of these patients. Primary location, T-stage and node status, disease-free interval, and number and size of metastases were associated with treatment failure. The area under the curve from the validation of the model was 0.6 (95% confidence interval 0.52-0.68). Patients with a high-risk of treatment failure (≥40%) had a worse survival from the landmark time of 12 months from surgery compared with those with low-risk (2-years: 82% vs. 70%; p=0.0002). Primary location, T stage, node status, disease-free interval, and number and size of metastases are associated with treatment failure. The survival of patients with a probability of treatment failure ≥40% is unfavorable. Future trials investigating the role of neoadjuvant therapy in these high-risk patients are warranted.

Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma.

We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.

Improving survival after pulmonary metastasectomy for sarcoma: analysis of prognostic factors.

Metastatic sarcoma confers a grave prognosis to patients and poses a management dilemma for clinicians. Pulmonary metastasectomy is frequently performed for the recurrence of sarcomatous tumours in the lung, but the evidence-base is poor. No guidelines exist to inform clinicians on appropriate patient selection and surgical technique. This review aims to establish and analyse the most important prognostic factors for survival post pulmonary metastasectomy for recurrent sarcoma. We summarise the key tumour, peri-operative and patient characteristics that should guide surgical management. A comprehensive search of the literature utilising OVID Medline and PubMed databases was conducted to identify all relevant research within the past 15years. We evaluated all articles that specifically studied sarcoma patients (both bone and soft tissue). Disease-free interval and tumour burden remain important prognostic factors, while tumour grade is likely not significant. VATS is a safe and viable alternative to thoracotomy without sacrificing survival outcomes. No single peri-operative characteristic provides useful prognostic information in isolation.

Prognostic significance of HPV16 infection in oral squamous cell carcinoma

Background/Aim: Many studies confirmed strong association between oncogenic genotypes of Human Papillomaviruses (HPVs) and some oropharyngeal and oral squamous cell carcinomas (OSCCs). The aim of this study was to determine the prognostic significance of HPV16 infection in OSCC in population of Montenegro i.e. correlation between HPV16 infection and disease free interval (DFI), disease recurrence and metastasis occurrence. Material and Methods: We examined surgically obtained specimens from 60 patients with OSCC (localized on the lower lip, tongue or/and floor of the mouth) in six years period. Tumor tissue samples were used for histological analysis and HPV16 genome PCR detection (primers for detection of E6 gene). Patients were followed up for the 3 years. Results: HPV16 infection was more commonly detected in females with OSCC (p=0.038), while no correlation between this infection and disease recurrence (p= 0.122) and/or metastasis occurrence (p= 0.934) was found. DFI was not significantly different between patients with or without HPV16 infection (p= 0.427), but DFI was significantly shorter (p= 0.003) in females with oral HPV16 infection compared to male patients with this infection. Conclusions: Counting that HPV16 infection has a negative prognostic significance in OSCC, the HPV immunization program against genital HPV infection, would also have a positive impact on the frequency of HPV-mediated OSCC in Montenegrin population.

Prognostic Factors for Cancer-Specific Survival and Disease-Free Interval of Dogs with Mammary Carcinomas.

Canine mammary tumors (CMTs) are the most diagnosed neoplasms in dogs; however, there are few studies analyzing the influence of epidemiological, clinicopathological, and histopathological data on cancer-specific survival (CSS), disease-free interval (DFI), and overall survival (OS) in a large cohort. To contribute to the understanding of the biological behavior of this neoplasm, 385 cases were analyzed, 89% malignant, 4% benign, and 7% non-neoplastic lesions. Among the dogs diagnosed with malignant neoplasms, 86% had early clinical stages (I-III), while 14% had regional or distant metastasis at the time of diagnosis. Carcinoma in a mixed tumor was the most frequent histological type with 44% of the cases and had the best prognosis. Analyzed factors such as the presence of pseudocyesis, previous history of the disease, advanced clinical stage (IV-V), and presence of ulceration obtained significant results for CSS, DFI, and OS through univariate analysis and had a negative impact on the survival of the patients. Multivariate analysis showed that histological grading and age proved to be the best independent parameters for the prognostic evaluation of CSS and DFI in this study. These factors were also significant in the overall survival analysis. Therefore, these parameters should be considered valuable risk and prognostic factors for CMTs.

L1CAM Is Not a Predictive Factor in Early-stage Squamous-cell Cervical Cancer.

Our study aimed to assess expression of L1 cell adhesion molecule (L1CAM) in early-stage cervical squamous-cell cancer as a prognostic factor. This retrospective, single-institution study included 154 patients who underwent radical hysterectomy for early-stage squamous cell cervical cancer between 2007 and 2017. Tumor samples from 154 patients were available for L1CAM analysis by immunohistochemistry. Among all patients, radical abdominal hysterectomy was performed in 144 cases. L1CAM expression was positive in 24 tumors (15.6%) of the whole group. In relation to the grade of differentiation and the presence of lymphovascular invasion, L1CAM expression did not show an association (p=0.154 and p=0.306, respectively). The disease-free interval and overall survival also did not significantly differ between L1CAM-positive and L1CAM-negative cases (p=0.427 and p=0.240, respectively). For histopathological characteristics, L1CAM-positive cases had a significantly higher median tumor size (p=0.015). Even in the selected group of 115 cases without nodal infiltration, L1CAM status had no effect on the relapse rate during follow-up. Our study did not confirm the results of previous studies showing L1CAM expression to be a negative prognostic factor in cervical cancer. In our study, increased L1CAM expression in early-stage squamous-cell cervical cancer was not associated with adverse prognosis regarding disease recurrence, disease-free survival, nor overall survival. L1CAM expression was correlated only with the size of the tumor.

Ekspresija survivina u oralnom skvamocelularnom karcinomu

Introduction: Survivin functions as an apoptosis inhibitor and a regulator of cell division. This study aimed to determine the correlation between survivin expression and clinicopathologic parameters of oral squamous cell carcinoma (OSCC) and determine its potential role in the progression/prognosis of this type of tumor. Materials and methods: Immunohistochemical analysis of survivin expression was performed on 45 surgically obtained paraffin-embedded tissue samples of OSCCs. Data on patients' gender, age, tumor grade, site and stage, disease recurrence, metastasis occurrence , and disease-free interval (DFI) were correlated to survivin expression. Results: Survivin immunoreactivity was observed in 77.8% of samples. No significant correlation between survivin expression and age (p = 0.087), gender (p = 0.334), tumor site (p = 0.175), presence of lymph node metastases (p = 0.201), or disease recurrence (p = 0.451) was found. Survivin expression was observed in well and moderately differentiated tumors and in all clinical stages (p = 0.139). Patients with low survivin expression had better survival rates than the group with medium and high survivin expression, i.e., there was a tendency of a shorter DFI in patients with higher expression of survivin (p = 0.065). Conclusion: There is a tendency for a shorter disease-free period in patients with higher survivin expression. These data suggest that survivin expression in OSCC may act as an additional prognostic parameter that indicates an increased proliferative tumor potential. To further validate survivin as a prognostic marker in OSCC, a study with a larger sample size along with clinical follow-up data is needed.

Clinical Features and Prognosis of Uncommon Metastatic Breast Cancer: A Retrospective Analysis of 82 Cases.

With the improvement of diagnostic techniques, numerous uncommon metastases derived from breast cancer were reported. However, very few studies explored the clinical characteristics and prognostic patterns of these patients. A total of 82 cases of uncommon metastatic breast cancer (MBC) registered at our hospital from January 1, 2010, to July 1, 2022, were selected for this retrospective study. The diagnoses of uncommon metastases were based on pathology, and the potential prognostic indicators (overall survival [OS], uncommon disease-free interval [uDFI], and remaining survival [RS]) were estimated. The uncommon metastases involved distant soft tissue, parotid gland, thyroid, digestive system, urinary system, reproductive system, bone marrow, and pericardium. Stepwise multivariate Cox regression analysis indicates age ≤ 35 is an independent risk factor of poor outcome of OS, uDFI, and RS in uncommon MBC patients. Meanwhile, uncommon metastasis combined with common visceral metastasis is an independent risk factor for poor RS of uncommon MBC patients, with a hazard ratio of 6.625 (95% confidence interval = 1.490-29.455, P = .013). Post hoc pairwise comparisons showed that uncommon MBC patients who developed bone-only metastasis survived longer than those concomitant with common visceral metastasis (P = .029). Although the incidence is low, uncommon MBC may involve multiple metastatic sites. The delayed diagnosis of uncommon metastases could lead to systemic progression of the disease. However, patients who only develop uncommon metastasis have a significantly better prognosis than that of those combined with common visceral metastasis. Even for those complicated by bone-only metastasis, active treatment of bone metastases can still achieve substantially longer survival.

Pattern of Care of Recurrent Cervical Cancer in Low-resource Settings: Challenges and Patient-initiated Follow-up as a Novel Opportunity.

The availability of optimum diagnostic strategies remains a major problem in resource-constraint countries. This technique of patient-initiated follow-up (PIFU) has been recently adopted in the UK for gynecological cancers and has proven cost benefits. However, no study from the Indian subcontinent has ever been reported. The primary objective was to study the pattern of care of recurrent cervical cancer in low-resource settings. The secondary objective was to compare the reliability of symptomatology/clinical evaluation and imaging methods on follow-up to detect recurrence and thus explore the feasibility of symptom-based PIFU. This was a single-institutional retrospective analysis of recurrent cervical cancer cases for a period of 3 years from January 2019 to January 2022. Patients who followed up for minimum of 6 months were included in the study. In 57 of the total 69 patients, symptoms alone were the index diagnostic method. Interestingly, neither of the methods of recurrence detection had impact on overall survival (OS). Cox regression analysis revealed adverse impact of erratic/lost to follow-up (hazard ratio [HR] = 3.8) and pelvic side wall disease (HR = 1.33) on survival. Patients with positive para-aortic nodes had significantly shorter disease-free interval of 11 months, so adding systemic therapy to adjuvant treatment in this cohort needs to be further investigated. Our analysis showed that patients with recurrence who were diagnosed with clinical manifestations alone vis-à-vis the ones who were diagnosed primarily on routine follow-up visit by some imaging or diagnostic test had comparable oncologic outcomes. PIFU can be a "practice changing modality" in patient management system, especially in low-resource settings. It will prove to be a simple cost-effective method to detect recurrence and prevent fallouts. Our study points to the feasibility of PIFU in Indian scenario.

Management of oligometastatic disease in soft tissue sarcomas

Oligometastatic soft tissue sarcoma represents an intermediate state between localized and disseminated disease. Combination A combination of surgery, radiotherapy and systemic treatment significantly improves prognosis, with a 5-year overall survival as high as 50%. Due to the high prevalence of lung metastases, most of the surgical evidence is centered around lung metastasectomy. The decision to perform surgical metastasectomy remains dependent on optimal patient selection. Adequate post-surgical lung function, absence of extrapulmonary metastases, control of the primary tumor, and feasibility of achieving negative margins are major criteria for patients to undergo successful surgery. Adequate margins, longer disease-free interval, unilateral, limited number (≤ 2), metachronous and small (&lt; 2 cm) pulmonary metastasis are some factors associated with improved survival. Radiotherapy, especially SBRT, is an effective treatment for disease control, and its use as (neo)-adjuvant therapy has shown promising results. However, studies comparing radiotherapy against surgery are missing and the efficacy of radiotherapy independent of surgery is not yet clear. Interventional radiology techniques such as percutaneous thermal ablation (PTA) or arterial embolization have also been described as potential treatment alternatives in candidates deemed not fit for surgery. Systemic treatment has traditionally consisted of an anthracycline (doxorubicin)-based regimen with the addition of ifosfamide in certain cases. Recent advances in systemic treatment include the use of targeted therapy and immunotherapy in (oligo)-metastatic STS. However, except for certain histologies, most STS subtypes are chemoresistant, and the response to systemic treatment is poor.

Treatment Outcome of Cervical Cancer Patients in the Elderly Population Aged 80 Years and Above: A Single Institution Study

Introduction: Age-related deficits such as malnutrition, functional reliance, and cognitive decline also occur in older women, as they are typically weaker and have many co-morbid conditions like diabetes or cardiac illness. These prognostic factors might predict overall survival and progression-free survival. Aim: To analyse the management outcomes of elderly patients with cervical carcinoma treated with radiotherapy and brachytherapy. Materials and Methods: A retrospective observational study was conducted in the Department of Radiation Oncology at Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India. Medical records were collected from 876 patients with cervical cancer who had been treated with radiotherapy or combined radiotherapy and chemotherapy from January 2009 to December 2021. A total of 876 patients presented with cervical cancer in the Outpatient Department (OPD), and 20 patients meeting the inclusion criteria were selected. Patients diagnosed with cervical cancer, Federation International Federation of Gynaecology and Obstetrics (FIGO) stage IB to IVA, aged equal to or greater than 80 years old, and Eastern Cooperative Oncology Group (ECOG) performance status I to III were considered for inclusion. Categorical variables were expressed as counts and percentages. The following clinicopathological characteristics of the study population were examined: FIGO staging, including stage IB to stage IVA, histopathological features of adenocarcinoma, squamous carcinoma, or adenosquamous carcinoma, doses of radiotherapy and brachytherapy, overall survival, disease-free survival, and the patient’s current status (alive or dead) was determined. If death occurred, the cause of death was determined. The Kaplan-Meier approach was used to analyse overall survival and disease-free survival in the study population using XLSTAT statistical software. Results: The study population was age standardised, with 18 patients (90%) falling between the ages of 80 and 85, and 2 patients (10%) falling between the ages of 86 and 90. A total of 12 patients (60%) belonged to ECOG PS II. A total of 19 (95%) patients had histologically confirmed squamous cell carcinoma. 75% of the population was in a locally advanced stage (stage III-IVA). The overall survival (in months) was 65.58 months, which was statistically significant (p&lt;0.0083). Similarly, the average disease-free interval was 38.73 months, which was also significant (p&lt;0.0062). Conclusion: According to the findings of the study, age may not be an independent risk factor for determining the outcome of cervical cancer patients in the Indian scenario. Even though elderly females may present with multiple co-morbidities, the standard treatment protocol must be radical.

The Outcome of Discontinuing Tyrosine Kinase Inhibitors in Advanced Sarcoma Following a Favorable Tumor Response to Antiangiogenics Therapy.

(1) Background: The use of antiangiogenic TKIs (AA-TKIs) has recently emerged as a major paradigm shift in the treatment of advanced sarcoma. However, the feasibility of drug holidays for patients demonstrating a very favorable response remains unknown. (2) Methods: We aim to explore the outcomes of patients with advanced sarcoma who discontinued AA-TKIs after a (near-) complete remission or were long-term responders. Patients with advanced disease were included if they had bilateral or multiple lung metastases, extrapulmonary recurrence, a short disease-free interval, etc., at the initiation of AA-TKIs. (3) Results: A total of 22 patients with AA-TKI discontinuation were analyzed, with a median follow-up of 22.3 months post-discontinuation. Prior to discontinuation, there were four drug-induced complete remissions (CRs), twelve surgical CRs, and six long-term responders. Disease progression was observed in 17/22 (77.3%) patients, with a median of 4.2 months. However, since the majority were still sensitive to the original AA-TKIs and amenable to a second surgical remission, 7 out of these 17 patients achieved a second CR after disease progression and were thus considered as relapse-free post-discontinuation (pd-RFS). Therefore, the pd-RFS and post-discontinuation overall survival (pd-OS) in the last follow-up were 12/22 (54.5%) and 16/22 (72.7%), respectively. Remarkably, surgical CR and drug tapering off (versus abrupt stopping) were associated with a greater pd-RFS and pd-OS (p < 0.05). Furthermore, higher necrosis rates (p = 0.040) and lower neutrophil-to-lymphocyte ratios (NLR) (p = 0.060) before discontinuation tend to have a better pd-RFS. (4) Conclusions: Our results suggest that AA-TKI discontinuation with a taper-off strategy might be safe and feasible in highly selected patients with advanced sarcoma. Surgical CR, NLR, and tumor necrosis rates before discontinuation were potential biomarkers for AA-TKI withdrawal.

Embryo Cryopreservation as an Alternative to Treat Infertility in Breast Cancer Survivors in Reproductive Age: Case Reports

Introduction: Chemotherapy has been shown to reduce breast cancer (BC) mortality significantly. However, several types of chemotherapy drugs affect the reproductive system. As BC has become increasingly prevalent, many young women are diagnosed during their reproductive years. As a result, overcoming chemotherapy-related infertility is becoming increasingly important. Hence, in-vitro fertilization (IVF) with embryo cryopreservation before chemotherapy is considered a way to preserve future reproductive potential. For this reason, this paper aims to report the cases of safe pregnancy in BC survivors through pre-chemotherapy IVF followed by embryo cryopreservation.Case Presentation: Two women, aged 35 and 29, respectively, were treated for BC by surgery, chemotherapy, and tamoxifen. They performed in-vitro fertilization (IVF) with embryo cryopreservation before chemotherapy. Their pregnancy was completed without complications, and they gave birth to healthy babies. Their last oncological visit also showed no signs of cancer recurrence, showing disease-free intervals of seven and eight years, respectively.Conclusions: Pre-chemotherapy IVF followed by embryo cryopreservation can be an alternative to treat infertility in BC survivors of reproductive age who are receiving chemotherapy.

Silencing of TMED5 inhibits proliferation, migration and invasion, and enhances apoptosis of hepatocellular carcinoma cells.

Transmembrane P24 trafficking protein 5 (TMED5) is highly expressed in cervical and bladder cancer cell lines. Moreover, TMED5 promotes nuclear autophagy and the malignant behavior of cervical cancer cells. However, the role of TMED5 in hepatocellular carcinoma (HCC) has not been extensively reported. To investigate the role of TMED5 in HCC cells. Bioinformatics was used to analyze the messenger-ribonucleic acid (mRNA) expression of TMED5 in HCC and its relationship with overall survival and disease-free interval of HCC patients. After TMED5 was decreased in SMMC-7721 and Hep3B cells, they were assayed for proliferation, cell cycle, apoptosis, migration, and invasion. The expression of TMED5 mRNA in HCC tissues was higher than in adjacent normal tissues, and the overall survival of HCC patients with high TMED5 transcription levels was worse. Moreover, the overexpression of TMED5 was associated with HCC progression. The downregulation of TMED5 suppressed cell proliferation, migration and invasion, and enhanced apoptosis. Therefore, TMED5 may be involved in the regulation of the cell cycle, the mammalian target of rapamycin signaling pathway, and the transforming growth factor beta (TGF-β) signaling pathway. The TMED5 has the potential to promote HCC progression. Therefore, lowering TMED5 levels could represent a potential strategy for the treatment of HCC.

Pancancer Analysis of the Prognostic and Immunotherapeutic Value of Progestin and AdipoQ Receptor 4.

AdipoQ receptor 4 (PAQR4) belongs to the family of progestin and AdipoQ receptors. PAQR4 plays an oncogenic role in lung and breast cancer. However, systematic pancancer analyses of PAQR4 have not been performed. The purpose was to investigate the prognostic and immunological significance of PAQR4 across 31 tumor types. Data were obtained from the following sources: TCGA, GEO, UALCAN, TIMER, GEPIA2, KM plotter, and TISIDB databases. The results proved that PAQR4 expression was significantly elevatory in most cancer types. We then explored the utility of PAQR4 as a prognostic indicator across all cancers. Using Cox proportional risk regression models, it has been demonstrated that PAQR4 is an independent risk factor in. High PAQR4 expression was not associated with other prognostic indicators, including overall survival, disease-free interval, disease-specific survival, and progression-free period. Subsequently, we explored the immunological value of PAQR4 and found that PAQR4 expression significantly correlated with tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoint genes in tumors. It also significantly negatively correlated with most tumors' ESTIMATE scores, indicating that PAQR4 can influence the cellular composition of the tumor microenvironment. Our findings suggest the immunotherapeutic potential of PAQR4 in tumors. Finally, we explored the role of PAQR4 in tumor drug resistance and found that PAQR4 expression affected the sensitivity to multiple chemotherapeutic agents. A significant role for PAQR4 in tumor immunity is evident in these studies, as well as its potential role in cancer diagnosis, prognosis, and treatment precision.

Survival and prognostic factors in oligometastatic breast cancer

BackgroundGuidelines for oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and local ablative treatment (LAT) of all lesions. The aim of this approach is prolonged disease remission, or even cure. Long-term outcomes in OMBC and factors associated with prognosis are largely unknown, due to the rarity of this condition. We report overall survival (OS), event-free survival (EFS), and prognostic factors in a large real-world cohort of patients with OMBC. MethodsPatients with breast cancer and 1–3 distant metastatic lesions, treated in the Netherlands Cancer Institute between 1997 and 2020, were identified via text mining of medical files. We collected patient, tumor and treatment characteristics. The Kaplan-Meier method was used to calculate OS and EFS estimates, and Cox regression analyses to assess prognostic factors. ResultsThe cohort included 239 patients, of whom 54% had ERpos/HER2neg, 20% HER2pos and 20% triple negative disease. Median follow-up was 88.0 months (95% confidence interval (CI) 82.9–93.1) during which 107 patients died and 139 developed disease progression/recurrence; median OS was 93.0 months (95%CI 66.2–119.8). Factors associated with OS in multivariable analysis were subtype, disease-free interval and radiologic response to first-line systemic therapy; LAT was associated with EFS, but not OS. ConclusionsIn this large real-world cohort of patients with OMBC, OS and EFS compare favorably to survival in the general MBC population. Radiologic complete response to first-line systemic therapy was associated with favorable OS and EFS, indicating the importance of early optimal systemic therapy. The value of LAT in OMBC requires further study.