True Recurrence Research Articles

Detection, Patterns, and Outcomes of Recurrent HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Recurrent human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is a relatively rare but serious disease with little empirical data. Previous works have studied patterns of recurrence in HPV-positive OPSCC, but only one has studied truly recurrent disease as opposed to persistent disease, and no work systematically analyzed posttreatment surveillance imaging strategies and how recurrences were detected. To refine the understanding of HPV-positive OPSCC recurrence and inform optimal imaging surveillance strategies. This retrospective cohort study involved electronic medical record review at a tertiary care hospital. Patients treated for OPSCC from 2012 to 2019 were extracted, and patients diagnosed with HPV-positive OPSCC were identified. Data were analyzed from December 2022 to May 2023. Percentage of patients with a true recurrence, location of recurrence, time of recurrence detection, and method of recurrence detection. Recurrence was demonstrated with a scan after an imaging-established disease-free state 3 to 6 months posttreatment. Of the 367 patients with HPV-positive OPSCC (mean [SD] age, 60.6 [9.2] years; 310 [84.5%] male), 37 (10.1%) experienced true disease recurrence. Median (IQR) follow-up time of the cohort was 3.6 years (8.5-88 months), defined as time from diagnosis to death or last contact. Within the true recurrence cohort, 21 patients (56.8%) experienced local, regional, or local and regional recurrence (LRR); 15 (40.5%) experienced distant metastasis (DM); and 1 (2.7%) experienced both LRR and DM. The mean (SD) time for detecting LRR was 2.46 (1.94) years and was considerably longer compared to the 1.89 (0.87) years for detecting DM (difference, 0.57 [95% CI, -0.29 to 1.02] years). The majority of patients identified their recurrence through symptom changes (31 [81.1%]) rather than through surveillance imaging (3 [8.1%]). In this cohort study, 10.1% of patients experienced true HPV-positive OPSCC disease recurrence, with most incidences of DM occurring in the lung and brain. Disease recurrence was identified primarily through symptomatic change, suggesting that further research may be needed to understand the optimal surveillance strategies after definitive treatment.

Cryoablation of Primary Breast Cancer in Patients Ineligible for Clinical Trials: A Multiinstitutional Study.

BACKGROUND. Breast cancer cryoablation clinical trials have strict inclusion criteria that exclude patients with potentially treatable disease. OBJECTIVE. The purpose of this study was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for prospective cryoablation clinical trials due to unfavorable patient or tumor characteristics. METHODS. This retrospective study included women who underwent cryoablation of biopsy-proven unifocal primary breast cancer with locally curative intent, without surgical excision, despite being ineligible for (and thus excluded from) cryoablation clinical trials, across seven institutions between January 1, 2000, and August 26, 2021. Adverse events (AEs) were recorded. Cryoablation procedures were classified as technically successful if they were not prematurely terminated and achieved intended treatment parameters and if the first follow-up imaging examination showed no evidence of residual disease. The results of follow-up biopsies were recorded. Ipsilateral breast tumor recurrences (IBTRs) diagnosed during follow-up were identified and classified as true recurrence or new primary disease. A competing-risk model was used to estimate the cumulative incidence of IBTR accounting for death before IBTR as a competing risk. RESULTS. The final study sample included 112 patients (median age, 71 years). A total of seven of 112 (6.3%) patients had a minor AE; no moderate or major AEs occurred. A total of 110 of 112 cryoablation procedures (98.2%) were technically successful. During a median follow-up of 2.0 years, 22 of 110 patients (20.0%) underwent biopsy for suspicious imaging findings in the ipsilateral breast, which yielded benign concordant findings in nine of 22 patients (40.9%) and IBTR in 12 of 22 patients (54.5%). Overall, 12 of 110 patients (10.9%) experienced IBTR, including seven with true recurrence and five with new primary disease; three of 12 patients (25.0%) with IBTR had received earlier adjuvant or neoadjuvant therapy. When death was accounted for as a competing risk, the cumulative incidence of IBTR was 5.3%, 12.2%, and 18.2% at 1, 2, and 3 years, respectively. CONCLUSION. In select individuals with unfavorable patient or tumor characteristics, breast cancer cryoablation provides a safe alternative to surgery and has good outcomes. These findings may be particularly relevant in patients who are also poor surgical candidates. CLINICAL IMPACT. Breast cancer cryoablation can be safely applied in a larger patient populations than those defined by clinical trial inclusion criteria.

Clinical and computed tomography outcomes after mesh-enforced hiatoplasty and anterior hemi-fundoplication in large hiatal hernia repair.

The surgical technique in large hiatal hernia (HH) repair is controversially discussed and the outcome measures and follow-up schemes are highly heterogeneous. The aim of this study is to assess the true recurrence rate using computed tomography (CT) in patients with standardized large HH repair. Prospective single-center study investigating the outcome after dorsal, mesh-enforced large HH repair with anterior fundoplication. Endoscopy was performed after 3months and clinical follow-up and CT after 12months. Between 2012 and 2021, 100 consecutive patients with large HH were operated in the same technique. There were two reoperations within the first 90days for cephalad migration of the fundoplication. Endoscopic follow-up showed a correct position of the fundoplication and no relevant other pathologies in 99% of patients. Follow-up CT was performed in 100% of patients and revealed 6% of patients with a cephalad slippage, defined as migration of less than 3cm of the wrap, and 7% of patients with a recurrent hernia. One patient of each group underwent subsequent reoperation due to symptoms. There was no statistical correlation between abnormal radiological findings and clinical outcomes with 69.2% of patients being asymptomatic. Multivariate logistic regression did not show any prognostic factor for an unfavorable radiologic outcome. Ninety-four percent of patients rated their outcomes as excellent or good. Radiological follow-up after large HH repair using CT allows to detect slippage of the fundoplication wrap and small recurrences. Patients with unfavorable radiological outcomes rarely require operative revision but should be considered for further follow-up.

Relapsed Bacterial Meningitis in an Adolescent Patient with Aberrant Patent Foramen Caecum

Bacterial meningitis is a serious life-threatening condition. Recurrent meningitis is defined as two independent episodes of meningitis that are separated by a period of convalescence and full recovery. Therefore, true recurrence results from a re-infection with the same or a different bacterial organism. In contrast, recrudescence and relapsed meningitis (RBM) represent persistence of the initial infection resulting from treatment failure. Both are uncommon and could be due to anatomic anomalies of the skull, traumatic head injury with secondary CSF fistula, complement deficiency or spread from a para meningeal infection.

Relapsed Bacterial Meningitis in an Adolescent Patient with Aberrant Patent Foramen Caecum

Bacterial meningitis is a serious life-threatening condition. Recurrent meningitis is defined as two independent episodes of meningitis that are separated by a period of convalescence and full recovery. Therefore, true recurrence results from a re-infection with the same or a different bacterial organism. In contrast, recrudescence and relapsed meningitis (RBM) represent persistence of the initial infection resulting from treatment failure. Both are uncommon and could be due to anatomic anomalies of the skull, traumatic head injury with secondary CSF fistula, complement deficiency or spread from a para meningeal infection.

Postoperative Outcomes of Bascom Cleft Lift Versus Excision With Secondary Wound Healing for Pilonidal Sinus Disease: A Multicenter Retrospective Analysis.

Pilonidal sinus disease impacts patient's quality of life. In the Netherlands, it is often treated with excision and secondary healing, which is associated with high recurrence rates and poor wound healing. The Bascom cleft lift, an alternative technique, has shown favorable healing times and recurrence rates. The present study aims to compare successful wound healing, time to healing, complications, and recurrence rate between excision with secondary wound healing and Bascom cleft lift. This is a multicenter retrospective study. Three institutions in the Rotterdam region of the Netherlands participated in the study. Patients who underwent excision with secondary healing or Bascom Cleft Lift between July 2015 and August 2021 were included. Primary endpoints included the rate of successful wound healing and the time to achieve healing. Secondary endpoints included postoperative complications and recurrence rate within twelve months after surgery. Out of 272 patients, 128 underwent Bascom cleft lift and 144 patients excision and secondary healing. Recurrent PSD (47.7% vs 22.2%) and abscess history (53.1% vs 40.3%) were more common in the Bascom cleft lift group compared to excision with secondary wound healing. The median follow-up period at the outpatient clinic was 43 days. Wound healing was 84.4% after Bascom cleft lift vs. 32.6% after excision and secondary healing (p < 0.001), with median time to wound healing of 55 days and 101 days, respectively (p < 0.001). Complications were 28.9% for Bascom cleft lift vs. 13.2% for excision and secondary healing (p = 0.003). Recurrent disease was 6.3% after Bascom Cleft Lift and 11.8% after excision and secondary healing (p = 0.113). It has a retrospective design which makes it prone to selection bias and residual confounding. Additionally, the study's short follow-up period further adds to these limitations as longer follow-up may better identify true recurrence rates. Finally, a deficiency is the absence of collected patient satisfaction data, which is nowadays a common scientific issue. This retrospective study shows that Bascom cleft lift is superior to excision and secondary healing given the higher percentage of patients with successful wound healing within a shorter time. See Video Abstract.

Abstract PO5-22-04: Genomic analysis of local recurrences following risk adapted breast radiotherapy in the IMPORT trials defines 'true recurrences' and 'new primaries'

Abstract Background: Most ipsilateral breast tumor recurrences (IBTR) following breast conserving surgery occur near the tumor bed (Veronisi et al, Ann Oncol 2001) and are considered to represent ‘true recurrence’ (derived from residual malignant cells of the index cancer). A smaller number occur elsewhere in the breast and are thought to be ‘new primaries’ (independently occurring cancer). The IMPORT LOW (Coles et al, The Lancet 2017) and IMPORT HIGH (Coles et al, The Lancet 2023) trials investigated adaptation of radiotherapy dose-volume to this spatially varying risk, testing partial breast irradiation and simultaneous integrated boost in patients with tumors at low and high risk of IBTR respectively. We analysed genomic relationships between index cancers and recurrences in these trials, to ascertain the frequency of true recurrences and unrelated new primaries, and their spatial distribution. Methodology: FFPE blocks were obtained from 137 patients who developed subsequent ipsi- or contralateral breast cancer: 66 from IMPORT HIGH and 71 from IMPORT LOW (4 with bilateral second cancers). DNA extracted from index and subsequent cancers underwent shallow whole genome sequencing (sWGS) using the Illumina NovaSeq 6000 system. Copy number profiles were derived from sWGS data using the R package QDNAseq(Scheinin et al, Genome Res 2014); those that failed QC criteria were removed. Relatedness of tumor pairs was determined using the R package Breakclone (Lips et al, Nat Genet 2022). This approach uses individual copy number aberration breakpoint position rather than events at chromosomal arm level. The p value cutoff for relatedness was 0.01; values between 0.01 and 0.05 were considered ambiguous. Researchers were blinded to clinical information prior to results. Results: In 80/137 tumor pairs both copy number profiles met QC criteria and clonal relationship could be ascertained. In total 26/80 were considered related, 20/80 ambiguous and 34/40 non-related (Table 1). 16/26 ipsilateral subsequent cancers in IMPORT HIGH were clonally related to the primary tumor and could be considered true recurrences. In 5/26 it was impossible to accurately call clonality as pairs shared only common copy number changes such as 1q or 8q gain and 16q loss. 5/26 were considered new primaries. In the lower risk IMPORT LOW cohort, subsequent cancers appear to have similar chances of being related or independent. As expected, most contralateral tumors in IMPORT LOW showed no evidence of a clonal relationship to the index tumors. In both trials an ambiguous subgroup of pairs shared some common copy number changes suggesting similar phenotype.5/14 contralateral tumors in IMPORT HIGH, in which some women were also at high risk of systemic relapse, shared very similar copy number profiles to the index tumor and may be metastases rather than new primaries. Discussion: A considerable number of tumors classed as IBTR appear genomically unrelated to the index cancer particularly in low risk cancer; this biology is relevant to clinical management both initially and at ‘recurrence’. The finding that 5/14 contralateral cancers in the high risk group appear to be clonally related suggests that some may be metastases. Results are being confirmed by targeted sequencing and will be correlated with recorded spatial and clinicopathological data and patient outcome. Future work will analyse spatial relationships more precisely using deformable image registration. *From the 77 patients with baseline circulating tumor DNA samples, 2 patients were excluded because their samples failed during assay quality control. Table. PIK3CA and ESR1 alterations detected in circulating tumor DNA at baseline and post abemaciclib treatment Citation Format: Sara Lightowlers, Maria Roman-Escorza, Elena Provenzano, Judith Bliss, Jason Carroll, H Y Charlie Chan, Clare Griffin, Joanne Haviland, Monica Jefford, Anna Kirby, Navita Somaiah, Mark Sydenham, Jenny Titley, John Yarnold, Charlotte Coles, Elinor Sawyer. Genomic analysis of local recurrences following risk adapted breast radiotherapy in the IMPORT trials defines 'true recurrences' and 'new primaries' [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 PO5-22-04.

Abstract PO1-07-07: Radiomics features for distinguishing true recurrence versus new primary tumor following breast-conserving treatment

Abstract Background Despite modern surgical and irradiation techniques, ipsilateral breast tumor recurrence (IBTR) accounts for 5-15% of all cancer recurrences in women treated with breast conservative treatment. Historically, the methods to define true recurrence (TR) and new primary tumor (NP) for IBTR mainly rely on clinical and pathological criteria, limiting the accuracy of the discerption and causing misclassification. This study aimed to develop a preoperative, noninvasive model for distinguishing IBTR by integrating clinicopathological review with paired dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) at diagnosis and following in-breast recurrence. MethodsWe retrospectively extracted radiomics features from MRI to develop a radiomic cohort of IBTR (n =46), among which all patients underwent paired preoperative DCE-MRI. This radiomic cohort was divided into a training cohort (n =27) and a validation cohort (n =19) with stratified random sampling. Classification of IBTR as TR or NP on the basis of tumor location, histologic subtype, estrogen receptor, and HER2 status was set as the gold standard. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression were utilized to perform radiomics feature selection and model training, respectively. The clinical utility of the model was determined via decision curve analysis (DCA). Results We selected three radiomics features (first-order feature Kurtosis from the first postcontrast phase on IBTR DCE-MRI, GLCM feature Imc2 from the first postcontrast phase on IBTR DCE-MRI, and the delta feature Correlation from the precontrast phase of the change between IBTR and primary tumor DCE-MRI) to develop an IBTR-classification predicting radiomic model, which performed well in the validation cohort (AUC 0.867, 95% confidence interval (CI) 0.694-1). Further investigation for sensitivity (73.3%) and specificity (100%) verified a favorable concordance between the radiomic classification and the conventional standard, with a diagnostic accuracy of 79%. Conclusions: Our study demonstrated the feasibility of the radiomics model in predicting IBTR classification and provided preoperative information about the nature of “recurrence”. This might have important implications in surgical approaches and multidisciplinary care for IBTR. Further efforts are needed to improve the reproducibility of radiomics features and models in multiple centers. Citation Format: Feilin Qu, Guan-Hua Su, Jin-Hui Li, Chao You, Zhi-Ming Shao. Radiomics features for distinguishing true recurrence versus new primary tumor following breast-conserving treatment [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 PO1-07-07.

Efficacy of radiation therapy in Japanese patients with positive margins after breast-conserving surgery.

Additional surgical resection is recommended after breast-conserving surgery if the surgical margin is pathologically positive. However, in clinical practice, radiation therapy is sometimes used instead for several reasons. Irradiation may be appropriate for some patients, but real-world data is still insufficient to establish it as standard treatment. We retrospectively investigated the status of local control in patients who received irradiation for positive margins. We investigated 85 patients with positive margins after curative partial mastectomy who were treated with irradiation instead of additional excision during the period 2006-2013. The patients received whole-breast irradiation (43.2-50Gy) using photon beams and additional tumour-bed boost (8.1-16Gy) using electron beams. Intrabreast tumour recurrence was defined as secondary cancer within the ipsilateral conserved breast. Surgical margin was defined as positive if tumour cell exposure was pathologically confirmed on the margin. Seven patients (8.2%) developed intrabreast tumour recurrence during a mean observation period of 119months. As to components of positive margin, 76 cases were positive for an intraductal component, of which seven (9.2%) developed intrabreast tumour recurrence. Meanwhile, all nine cases positive for an invasive component were free from intrabreast tumour recurrence. Two of the intrabreast tumour recurrence cases seemed to develop new lesions rather than recurrence, considering tumour location. The cumulative incidence of intrabreast tumour recurrence over 10years was 6.1%. Limited to true recurrence, intrabreast tumour recurrence incidence was 4.9%. Our real-world data supports irradiation as an alternative to additional surgical intervention for positive margins after breast-conserving surgery and offers a basis for further research.

Trigeminal Neuralgia and Hemifacial Spasm: What to Do If It Does Not Cure?

Although microvascular decompression(MVD)is a highly effective treatment, there is little pathological evidence and some aspects of its mechanism remain unclear. Therefore, when symptoms appear after surgery, it is difficult to determine the pathological condition and select the treatment method. Therefore, we recommend dividing these factors into three categories. The first is "prolonged cure." Compressed nerves may take time to regenerate; therefore, it is necessary to wait at least one year to see if they recover naturally, especially in facial spasms. The second is "uncured." Intraoperative video and postoperative imaging findings should be reviewed. If a compressed blood vessel is overlooked or inappropriately decompressed, additional surgery should be performed. The third is "true recurrence," which is the loss of fixation of compressed blood vessels and granulomatization of the Teflon. Nerve bending that occurs again due to the retraction of the trigeminal nerve is corrected by reoperation. The therapeutic effects of reoperation are particularly strong in trigeminal neuralgia. Owing to the risk of nerve damage due to adhesion dissection, it is important to carefully consider and establish good communication with patients before surgery.

INNV-32. RELIABILITY OF SERIAL NEUROPATHOLOGICAL ASSESSMENT TO DIFFERENTIATE TUMOR PROGRESSION FROM PSEUDO-PROGRESSION IN GLIOMA

Abstract Histopathology is the gold standard for distinguishing tumor recurrence from treatment-induced necrosis but differentiating pseudoprogression from true recurrence is challenging in tumors with ambiguous morphological features. Prior research reported a 36% inter-rater agreement during suspected recurrence (Holdhoff et al., 2019). While serial radiographic and laboratory assessments are common, serial histopathological assessments are not. This study evaluated agreement and factors influencing assessment of active and inactive tumors through single and multiple time-point histopathological assessments. Patients who underwent initial and subsequent reoperation were identified, and their available histology slides were examined retrospectively. Four independent neuropathologists conducted two types of reviews: single time-point reviews using most recent biopsy/surgery slides, and multiple time-point reviews comparing images from initial and repeat biopsies taken 1-3 months apart. Neuropathologists completed a questionnaire assessing various tumor characteristics. Assignments were categorized as "active tumor," "treatment effect," or "unable to classify." 324 assessments were conducted (108 single time-point, 216 multiple time-point). Intraclass correlation coefficients for single vs. multiple time-point assessments were 0.72-0.93 for active tumors and 0.57-0.86 for inactive tumors. Pathologists' assessment of % inactive tumor was influenced by mitotic activity (p= 0.0028), cellularity (p&amp;lt; 0.0001), hyalinized vessels (p= 0.0019), and necrosis (p= 0.0046). Evaluation of % active tumor was influenced by hyalinized vessels (p= 0.0006), mitotic activity (p&amp;lt; 0.0001), cellularity (p&amp;lt; 0.0001), and microvascular proliferation (p= 0.0093), with the latter three factors specifically affecting final sign-out pathology. Serial histopathological assessment didn’t affect determination of % active or inactive tumor. No association between % inactive tumor and fibrinoid necrosis for single time-point (p= 0.34) but a strong negative association was seen for serial assessment (p= 0.0006). Inter-rater agreement was higher for identifying active tumors than inactive tumors in both case reviews. Changes in necrosis between tissue samples in single vs. multiple timepoint assessments influenced pathologists' assessment of % inactive tumor.

NCMP-12. PREVALENCE OF RADIONECROSIS IN RECURRENT GLIOBLASTOMA

Abstract INTRODUCTION Glioblastoma (GBM) standard treatment consists of maximum and safe surgical resection, followed by radiation therapy in combination with temozolomide. Some patients show radiological and/or clinical deterioration soon after radiotherapy treatment. Early MRI changes, in the first 3 months following radiation is considered pseudo-progression. After this initial period, changes are considered as tumor recurrence. However, cases of early radiological deterioration have been related to radionecrosis. When tumor progression is suspected on imaging, it may causes treatment withdrawal or change. Therefore, for a certain percentage of patients, effective treatment could be abandoned in the presence of radionecrosis. METHODS The aim of the study is to assess the prevalence of radionecrosis at the Hôpital de l'Enfant-Jésus. This is a retrospective, observational case-control study evaluating recurrent GBM patients who underwent a second resection surgery. RESULTS The charts of 110 GBM patients with second resection were retrospectively reviewed (men: 62%, mean age: 58.3 years). Among these patients, we observed 87 cases of GBM recurrence as compared to 23 cases of radionecrosis (21%). No statistically significant difference was observed between the two groups regarding demographics, survival, Karnofsky performance status, type of surgery and treatments received. However, in the radionecrosis group, decreases in time between the 2 surgeries (55.3 vs. 24.3 weeks, p = 0.006) and in the number of cycles of chemotherapy received (5.7 vs. 3.7 weeks, p = 0.004) were observed as compared to GBM group. CONCLUSIONS This study characterizes demographically the patients with second surgery for suspicion of GBM in order to better adapt the treatments. Clinical and radiological data could not differentiate radionecrosis from true tumor recurrence or progression. A prospective study will be carried out as a second step, in order to determine radiological or molecular factors that could predict the presence of radionecrosis.

The Controversy and Value of Mohs Micrographic Surgery for Melanoma and Melanoma in Situ on the Trunk and Extremities.

The use of Mohs surgery for melanoma on the trunk and extremities is not supported in the guidelines of dermatology, but is widely used in the real world. The purpose of this article is to expose the value of Mohs surgery for melanoma on the trunk and extremities for consideration of updating the guidelines. This was a retrospective review of a prospectively maintained database 7 to identify patients whose melanomas would likely have recurred using standard surgical margins. A prediction model was used to evaluate the value of Mohs surgery. The model predicted that 2,847 (2%) patients with melanoma on the trunk and extremities would likely recur each year with standard surgical margins even after re-excision when positive margins were identified, compared with 0.1% after Mohs surgery. This likely would result in the upstaging of 27% of melanoma in situ patients and 13% of patients with invasive melanoma. The upstaging would also result in a decrease in melanoma-specific survival and the death of 1% of patients with true local recurrences of melanoma. Mohs surgery has value for melanoma on the trunk and extremities by minimizing local recurrence and death from disease progression.

Intra-Operative Radiotherapy (IORT) in Breast Conserving Therapy in Early-Stage Breast Cancer and DCIS

Initial breast intra-operative radiotherapy (IORT) results in clinical trials were encouraging though with longer follow up, increased local recurrences have been reported compared with whole breast radiation or other partial breast radiation including accelerated partial breast irradiation (APBI) methods. The goal of the study is to report our prospective single institution IORT breast study outcomes of local recurrence (LR) including true recurrence and breast elsewhere failures, breast cancer specific survival (BCSS), and overall survival (OS) with low energy x-ray IORT in early-stage breast cancer or ductal carcinoma in situ. A total of 480 patients with early-stage breast cancer or DCIS were prospectively enrolled in an IRB approved single institution trial and treated with low energy X-ray IORT 20 Gy at time of breast-conserving surgery. Eligibility criteria included ≥ 45 years of age with unifocal tumors < 3 cm deemed candidates for partial mastectomy. Supplemental external beam radiation was recommended for patients with high-risk surgical pathology including multifocal disease, positive nodes, close margins < 2 mm, or lymphovascular invasion. Ipsilateral breast tumor recurrences were classified as true recurrence versus elsewhere failure by location and histology: same/different quadrant and similar/different histology. Kaplan-Meier methods were used to estimate survival probabilities across time. Median age of enrolled patients was 64 years with the majority of patients having favorable phenotype with 94% ER+ and 93% Her-2 - disease. 110 patients (23%) had supplemental EBRT delivered; 103 to the whole breast and 7 to the breast and regional nodes. At a median follow up of 73 months (range 17 - 131 months), there were 23 (4.8%) ipsilateral breast tumor recurrences, of which 9 were true recurrences (1.9%) and 14 elsewhere failures (2.9%). One patient with true recurrence and 3 patients with elsewhere breast failures synchronously presented with clinical or radiographic regional node involvement. Seven patient developed contralateral breast cancer and 8 patients developed distant metastases during the follow-up period. There were 2 breast cancer related deaths. At 6-years, overall survival rate was 96.8% and breast cancer specific survival was 98.7%. Our study outcomes reflect similar outcomes as other reported IORT studies with electron or low energy X-ray in breast cancer, with higher risk of local failure than historical whole breast and other partial breast radiation techniques. This supports current radiation society guidelines for IORT monotherapy for breast cancer to be optimally considered in the context of prospective clinical trials.

RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis.

Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.

The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy.

Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported. To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy. A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated. Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET. True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.

Initial Experience of 18 F-FET PET-MR Image Fusion for Evaluation of Recurrent Primary Brain Tumors.

Background An accurate monitoring technique is crucial in brain tumors to choose the best treatment approach after surgery and/or chemoradiation. Radiological assessment of brain tumors is widely based on the magnetic resonance imaging (MRI) modality in this regard; however, MRI criteria are unable to precisely differentiate tumoral tissue from treatment-related changes. This study was conducted to evaluate whether fused MRI and O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) positron emission tomography (PET) can improve the diagnostic accuracy of the practitioners to discriminate treatment-related changes from true recurrence of brain tumor. Methods We retrospectively analyzed 18 F-FET PET/computed tomography (CT) of 11 patients with histopathologically proven brain tumors that were suspicious for recurrence changes after 3 to 4 months of surgery. All the patients underwent MRI and 18 F-FET PET/CT. As a third assessment, fused 18 F-FET PET/MRI was also acquired. Finally, the diagnostic accuracy of the applied modalities was compared. Results Eleven patients aged 27 to 73 years with a mean age of 47 ± 13 years were enrolled. According to the results, 9/11 cases (82%) showed positive MRI and 6 cases (55%) showed positive PET/CT and PET/MRI. Tumoral recurrence was observed in six patients (55%) in the follow-up period. Based on the follow-up results, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64, 85, 25, 67, and 50%, respectively, for MRI alone and 91, 85, 100, 100, and 80%, respectively, for both PET/CT and PET/MRI. Conclusion This study found that 18 F-FET PET-MR image fusion in the management of brain tumors might improve recurrence detection; however, further well-designed studies are needed to verify these preliminary data.

Multimodality MRI Radiomics Based on Machine Learning for Identifying True Tumor Recurrence and Treatment-Related Effects in Patients with Postoperative Glioma.

Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR. A total of 131 patients were enrolled and randomly divided into the training set (n=91) and the test set (n=40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance. The PoE model had a significantly higher area under curve (AUC) than the ED model (p<0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models. Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence. 2021.04.15, No:2020039.

The Belsey Mark IV procedure in the era of minimally invasive antireflux surgery.

Different surgical techniques exist in the treatment of giant and complex hiatal hernia. The aim of this study was to identify the role of the Belsey Mark IV (BMIV) antireflux procedure in the era of minimally invasive techniques. A single-center, retrospective cohort study was conducted. All patients who underwent an elective BMIV procedure aged 18years or older, during a 15-year period (January 1, 2002 until December 31, 2016), were included. Demographics, pre-, per- and postoperative data were analyzed. Three groups were compared. Group A: BMIV as first procedure-group B: BMIV as a second procedure (first redo intervention)-group C: patients who had two or more previous antireflux interventions. A total of 216 patients were included for analysis (group A n = 127; group B n = 51; group C n = 38). Median follow-up in groups A, B and C was 28, 48 and 56months, respectively. Patients in group A were older and had a higher American Society of Anesthesiologists score compared to groups B and C. There was zero mortality in all groups. The severe complication rate of 7.9% in group A was higher compared with the 2.9% in group B and 3.9% in group C. Long-term outcome showed true recurrence, defined as both radiographic recurrence as well as associated symptoms, in 9.5% of cases in group A, 24.5% in group B and 44.7% in group C. The BMIV procedure is a safe procedure with good results, moreover in the aging and comorbid patient with primary repair of a giant hiatal hernia.

Racial Disparities in the Ascertainment of Cancer Recurrence in Electronic Health Records.

There is growing interest in using computable phenotypes or proxies to identify important clinical outcomes, such as cancer recurrence, in rich electronic health records data. However, the race/ethnicity-specific accuracies of these proxies remain unclear. We examined whether the accuracy of a proxy for colorectal cancer (CRC) recurrence differed by race/ethnicity and the possible mechanisms that drove the differences. Using data from a large integrated health care system, we identified a stratified random sample of 282 Black/African American (AA), Hispanic, and non-Hispanic White (NHW) patients with CRC who received primary treatment. Patient 5-year recurrence status was estimated using a utilization-based proxy and evaluated against the true recurrence status obtained using detailed chart review and by race/ethnicity. We used covariate-adjusted probit regression models to estimate the associations between race/ethnicity and misclassification. The recurrence proxy had excellent overall accuracy (positive predictive value [PPV] 89.4%; negative predictive value 96.5%; mean difference in timing 1.96 months); however, accuracy varied by race/ethnicity. Compared with NHW patients, PPV was 14.9% lower (95% CI, 2.53 to 28.6) among Hispanic patients and 4.3% lower (95% CI, -4.8 to 14.8) among Black/AA patients. The proxy disproportionately inflated the 5-year recurrence incidence for Hispanic patients by 10.6% (95% CI, 4.2 to 18.2). Compared with NHW patients, proxy recurrences for Hispanic patients were almost three times as likely to have been misclassified as positive (adjusted risk ratio 2.91 [95% CI, 1.21 to 8.31]). Higher false positives among racial/ethnic minorities may be related to higher prevalence of noncancerous lung-related problems and substantial delays in primary treatment because of insufficient patient-provider communication and abnormal treatment patterns. Using a proxy with worse accuracy among racial/ethnic minority patients to estimate population health may misdirect resources and support erroneous conclusions around treatment benefit for these patients.