Unifocal Disease Research Articles

Impact of multifocal or multicentric disease on local recurrence and survival in breast cancer patients with or without BRCA1/2 variants

Multifocal or multicentric (MFMC) breast cancer is mainly focused on breast cancer patients with unknown BRCA status, the incidence and clinical relevance of MFMC disease in BRCA1/2 carriers is less explored to date. Our study was to investigate the incidence of MFMC disease in BRCA1/2 carriers and whether MFMC disease influences local recurrence and clinical outcomes. In this retrospective study, 479 breast cancer patients with BRCA1/2 variants and 1437 age-matched noncarriers were enrolled and patients received either breast-conserving therapy (BCT) or mastectomy with or without radiotherapy. The rates of MFMC disease in BRCA1 and BRCA2 carriers, and noncarriers were 33.0% (61 of 185), 37.4% (110 of 294), and 31.2% (449 of 1437), respectively. MFMC disease in BRCA2 carriers was significantly higher than that in noncarriers (P = 0.039). After a median follow-up of 8.1years, among patients treated with BCT, BRCA2 carriers with MFMC disease experienced a significantly higher rate of ipsilateral breast tumor recurrence (IBTR) than those with unifocal disease (16.7% vs 4.1%, P = 0.044). Moreover, BRCA2 carriers with MFMC disease had a significantly worse RFS (unadjusted hazard ratio [HR], 3.65 [95% CI 1.40-9.52]; P = 0.008), DRFS (unadjusted HR, 3.07 [95% CI 1.07-8.80]; P = 0.037), and OS (unadjusted HR, 4.96 [95% CI 1.18-20.02]; P = 0.029) than those with unifocal disease when treated with BCT. MFMC breast cancer is more common in BRCA2 carriers, and BRCA2 carriers with MFMC disease treated with BCT exhibit a higher rate of IBTR and may have a poor survival.

Evaluating the benefit of surgical resection for hepatocellular carcinoma with multifocality or intrahepatic vascular invasion

BackgroundThe role of hepatectomy for hepatocellular carcinoma (HCC) with multifocality or intrahepatic vascular involvement remains ill-defined. Our objective was to evaluate benefits of surgical resection for patients with these high-risk features. MethodsThe National Cancer Database was used to identify HCC patients with vascular involvement and/or multifocality (T2/T3, N-/M−) from 2011 to 2015. Propensity score matching (k-nearest neighbors, no replacement, 1:1) grouped patients by treatment: surgical resection versus non-surgical modalities. Groups were matched using patient, clinical, and liver-specific characteristics. Median overall survival (OS) was calculated using Kaplan–Meier, and adjusted analyses were performed using shared frailty models. Results14,557 patients met inclusion criteria, including 1892 (9.4%) treated with surgical resection. Median cohort OS was 20.5 months. After adjustment, surgical resection was associated with survival advantage compared to non-surgical treatment (37.8 versus 15.7 months, log-rank P < .001; adjusted hazard ratio 0.49, 95% confidence interval, 0.45–0.54). Patients with minimal comorbidity, unifocal disease, and age <54 had highest probability of survival one year post-surgery. ConclusionsSurgical resection is associated with a survival advantage in HCC with multifocality and/or intrahepatic vascular involvement. The presence of these features should not contraindicate consideration of hepatectomy in suitable surgical candidates.

The epidemiological and clinicopathological characteristics of multifocal/multicentric breast cancer in the Egyptian Delta and its impact on management strategies.

Multifocal (MFBC)/multicentric (MCBC) breast cancer is being more recognized due to the improved imaging modalities and the greater orientation with this form of breast cancer, however, optimal surgical treatment, still poses a challenge. The standard surgical treatment is mastectomy, however, breast-conserving surgeries (BCS) may be appropriate in certain situations. A total of 464 cases of MF/MCBC out of 4798 cases of breast cancer were retrospectively analyzed from the database of the Oncology Center, Mansoura University (OCMU), between January 2008 and December 2019. Radiologic involvement of multiple quadrants was reported in 27.9% by ultrasonography, 19% by mammography, and 59.1% by magnetic resonance imaging. BCS was performed in 32 cases (6.9%) while 432 cases underwent a mastectomy. Postoperative pathology revealed infiltration of other quadrants grossly in 23.5%, and under the microscope in 63.6% of the examined cases. Mean disease-free and overall survival were 95.5 and 164.6 months, respectively. When compared with MFBC, MCBC showed higher pathologic tumor size (p <0.001), higher stages (p <0.001), higher recurrence rates (p =0.006), and lower DFS (P =0.009) but with similar OS (P =0.8). Mastectomy is still the primary treatment option for MCBC with higher recurrence rates compared with MFBC. However, BCS for properly selected MFBC is considered oncologically safe, following the same rules of breast conservation for unifocal disease.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

NIMG-98. IDENTIFYING PATTERNS OF FAILURE AFTER INITIAL THERAPY IN PRIMARY CNS LYMPHOMA IN A LARGE PATIENT COHORT

Abstract INTRODUCTION Treatment of primary CNS lymphoma (PCNSL) has rapidly evolved, emphasizing improved efficacy while reducing neurotoxicity. PCNSL has historically been considered a multifocal disease and many patients relapse after first-line therapy. We evaluated relapse patterns in a large cohort of contemporarily treated patients. METHODS Consecutive PCNSL patients treated at MSKCC between 1983-2020 were analyzed. T1 post-contrast-enhancing disease on baseline MRI was characterized. Site of initial relapse was characterized as purely local (involving/adjacent to initial site) vs distant intraparenchymal, or other (e.g., both local and distant, systemic, ocular). Progression-free survival (PFS) was evaluated using Kaplan Meier methods. RESULTS Of 645 patients, 564 were eligible for analysis (diffuse large B-cell histology, sufficient data, ≥ 1 MRI response assessment). Median follow-up was 2.7 years (IQR 1.2-5.6). Median age was 63 years (range 19-90). Baseline disease was often supratentorial (420, 74%), multifocal (274, 49%), and bilateral (224, 40%). Fewer had leptomeningeal disease (94/430 CSF+, 22%; 117/559 radiographically positive, 21%). Most received methotrexate (MTX)-based induction (534, 96%), most commonly rituximab, MTX, procarbazine, vincristine (R-MVP; 257, 46%) or MVP (144, 26%). Overall, 286 (51%) patients relapsed with a median PFS of 2.1 years (95% CI 1.8-2.5). Of 275 characterizable relapses, 75 (27%) were exclusively local intraparenchymal, 91 (33%) were distant intraparenchymal, and 109 (40%) were other. Baseline unifocal disease often relapsed unifocally (66/118 baseline unifocal; 56%). Of 126 unifocal relapses, 45 (36%) were local. Of 202 patients with baseline supratentorial disease, 152 (75%) relapsed supratentorially. Unilateral relapses often remain ipsilateral (49% left- and 54% right-hemispheric lesions at baseline and relapse). CONCLUSIONS In a large PCNSL cohort, relapses often maintained baseline characteristics. For a disease historically considered multifocal, a substantial proportion of relapses were local. Future analyses will evaluate predictors of relapse, which can further efforts in informing personalization of treatment in the era of cellular therapies.

Primary Hyperparathyroidism: Is Image Localization Alone Sufficient to Ensure Long-Term Cure in Unifocal Disease?

Advances in imaging have facilitated precise preoperative localization and focused resection of hyperfunctional parathyroids in primary hyperparathyroidism (PHPT). Combining imaging techniques or a "dual" approach, when concordant, improves adenoma-localizing accuracy above individual modalities. This study sought to assess biochemical cure and failure rates (persistence or recurrence) of surgery directed by dual imaging alone in PHPT. This observational, single-center analysis comprised 31 patients diagnosed with PHPT and imaged with both ultrasound (USG) of theneck and sestamibi scintigraphy. The extent of surgery was based solely on inter-modality concurrence for adenoma localization; imaging-concordant patients underwent focused parathyroidectomy, whereas discordant patients necessitated neck exploration (with extent altered according to scintigraphic lesion lateralization). No intraoperative localizing adjuncts were used. Twenty-three patients had concordant imaging, of which 19 underwent focused exploration, with sensitivity and positive predictive value (PPV) for dual imaging of 100% and 95.7%, respectively. The overall sensitivity and PPV were 92.9% and 89.7% for USG aloneand 100% and 93.6% for scintigraphy, respectively. The mean age and prevalence of thyroid disease were significantly higher in the discordant group. All patients achieved postoperative normocalcemia. There were no cases of persistent or recurrent hyperparathyroidism on follow-up. In the imaging-concordant setting, focused surgery may be safely performed with the omission of other adjuncts for localization. Older age and concomitant thyroid pathology predispose to discordant imaging and are risk factors for surgical failure when attempting an image-directed approach. Neck exploration is an alternative in these patients with excellent cure rates and acceptable morbidity.

Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer.

PurposeSentinel lymph node (SLN) biopsy (SLNB) is the standard tool to stage the axilla of breast cancer patients. This study aimed to identify the predictors of positive SLNB in patients with clinically node-negative breast cancer.Patients and MethodsA retrospective, single-institution cohort of patients with early-stage breast cancer without clinically identifiable axillary lymphadenopathy was chosen from January 2010 to December 2018. Logistic regression was used to identify possible predictors of positive SLNB.ResultsFour hundred and seventy patients were identified; their mean age was 50±11 years. Most patients had the following characteristics: invasive ductal carcinoma (n=382, 81.3%), unilateral tumor (n=461, 98.1%), unifocal disease (n=351, 74.7%), intermediate grade (n=276, 59.0%), and estrogen and progesterone receptor positivity with human epidermal growth factor receptor 2 negativity (n=305, 64.9%). The mean size of the breast mass was 2.3±1.5 cm. SLNB was positive in 128 (27.2%) cases. The mean number of SLNs was 2±1.2. Axillary lymph node dissection was performed in 109 patients. The mean number of lymph nodes removed was 15±6. In 66 (60.6%) of the 109 patients with metastatic axillary nodes, only the SLNs were found to be positive. The number of SLNs, tumor size, tumor grade, receptor status, prominent axillary lymph nodes, and lymphovascular invasion predicted positive SLNB (P = 0.01, 0.03, 0.03, and 0.04 and <0.001 and <0.001, respectively).ConclusionOur results suggest that a number of histopathological and radiological characteristics of breast cancer can predict SLNB positivity in clinically node-negative breast cancer patients.

Abstract 5178: Multifocality is an independent predictor of regional lymph node metastasis in Middle Eastern papillary thyroid carcinoma

Abstract Background: Papillary thyroid carcinoma (PTC) is treatable, with favorable prognosis and very low disease-specific mortality. However, PTC recurrence is relatively common in loco-regional and distant sites. Although multifocality is a common occurrence in PTC, its prognostic impact remains controversial. In addition, data on prevalence and prognostic significance of multifocality in PTC from Middle Eastern ethnicity is unknown. Therefore, the aim of this study was to investigate the prognostic value of multifocality in PTC larger than 1cm and papillary thyroid microcarcinoma (PTMC) in our center. Methods: A cohort of 1515 patients who underwent total thyroidectomy were retrospectively reviewed. Aggressive histopathologic variants of PTC were excluded to avoid their potential confounding effect on clinical outcomes. We identified 1087 patients who had PTC with primary tumor exceeding 1cm and 150 patients with PTMC, with medium follow up of 9.2 years. In each group, we compared patients with unifocal and multifocal disease. Clinico-pathological and molecular correlations were analyzed. Logistic regression analysis was used to assess the relation between multifocal tumors and lymph node metastasis. Results: The incidence of multifocality in PTC larger than 1cm was 48.3% (525/1087), whereas it was 38.7% (58/150) in PTMCs. In patients with PTC &amp;gt; 1cm, multifocality was significantly associated with aggressive markers such as extrathyroidal extension (p &amp;lt; 0.0001), lymphovascular invasion (p = 0.0047), lymph node (LN) metastasis (p = 0.0006), distant metastasis (p = 0.0305) and BRAF mutation (p = 0.0113). In analogous analysis of patients with PTMC, multifocality was significantly associated with extrathyroidal extension (p &amp;lt; 0.0001), LN metastasis (p = 0.0005) and BRAF mutation (p = 0.0006). In both sub-groups, disease recurrence and overall survival did not differ between unifocal and multifocal group. Multivariate analysis showed that multifocality was an independent predictor of LN metastasis (Odds ratio (OR) = 1.31; 95% confidence interval (CI) = 1.00 - 1.71; p = 0.0472 for PTC &amp;gt; 1cm and OR = 1.88; 95% CI = 1.00 - 3.54; p = 0.0491 for PTMC). Conclusions: Tumor multifocality is frequently observed in Middle Eastern PTC and PTMC and is a predictive factor for LN metastasis in PTC. Given the predictive value of multifocality in Middle Eastern ethnicity, aggressive therapy and intensive follow-up should be considered for both PTC and PTMC with multifocality. Regional LN metastasis should be closely monitored and prophylactic central lymph node dissection could be considered in these patients. Citation Format: Pratheeshkumar Poyil, Abdul K Siraj, Sandeep Kumar Parvathareddy, Divya Padmaja, Saravanan Thangavel, Rafia Begum, Roxanne Diaz, Khadija Al-Obaisi, Khawla S. Al-Kuraya. Multifocality is an independent predictor of regional lymph node metastasis in Middle Eastern papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5178.

Whole-body magnetic resonance imaging findings and patterns of chronic nonbacterial osteomyelitis in a series of Greek pediatric patients.

Background:Chronic nonbacterial osteomyelitis (CNO) is a pediatric autoinflammatory disorder presenting with sterile inflammatory bone lesions. Whole-body MRI (WBMRI) has most recently emerged for disease assessment, but data are limited.Purpose:The purpose is to evaluate the imaging findings and patterns of CNO on WBMRI in a series of Greek pediatric patients.Material and Methods:Whole-body magnetic resonance imaging studies of all children with documented CNO, performed in a single tertiary center, were retrospectively reviewed. WBMRI included coronal T1 and short-tau inversion recovery (STIR), whole spine sagittal STIR, and ankle/foot sagittal STIR images. High signal intensity lesions on STIR images corresponding to bone marrow edema were recorded. The SPSS v.20 statistical package was used for descriptive statistics.Results:Twenty children were included (mean age: 12, range: 6–16 years) with 1–31 lesions (mean: 11.8) on WBMRI. Two children had unifocal disease localized at the clavicle, three paucifocal (1–4 lesions), and 15 multifocal bone involvement. All but two children presented with ankle pain and exhibited lesions at the bones of the ankle joint (90%) followed by the knee (50%) and pelvis (10%). The tibia was the most frequently affected bone (70%) followed by calcaneus (60%), fibula (50%), femur (45%), talus, and metatarsals (45%). No lesions in the cervical, thoracic, lumbar spine, and mandible were documented. Only small sacral lesions were seen in 25% of patients with the extensive peripheral disease. Bilateral metaphyseal and epiphyseal involvement with transphyseal extension were common, but the periosteal reaction and well-defined lesion margins were rare.Conclusion:Frequent involvement of the foot and ankle and paucity of substantial spinal involvement were seen in Greek pediatric patients with CNO.

Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial

The optimal management of vulvar high-grade squamous intraepithelial lesions (vHSILs) is challenging. Surgery is the standard treatment, but recurrences are observed in half of patients. Medical treatment with imiquimod is an effective alternative, but the two modalities have not been compared in a randomised trial. The aim of this study was to compare the clinical effectiveness, histological response, human papillomavirus (HPV) clearance, acceptance, and psychosexual morbidity of primary imiquimod treatment versus surgical treatment in women with vHSIL. This study was a multicentre, randomised, phase 3, non-inferiority clinical trial done by the Austrian Gynaecological Oncology group at six hospitals in Austria. We recruited female patients aged 18-90 years with histologically confirmed vHSIL with visible unifocal or multifocal lesions. Main exclusion criteria were clinical suspicion of invasion, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, and any active treatment for vHSIL within the previous 3 months. Women with known immunodeficiency, who were pregnant, or who were lactating were excluded. Patients were randomly assigned (1:1) by block randomisation to imiquimod or surgery, and stratified by unifocal or multifocal disease. Treatment with imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for a period of 4-6 months. Surgery consisted of excision or ablation. Patients were assessed with vulvoscopy, vulvar biopsy, HPV tests, and patient-reported outcomes at baseline and after 6 months and 12 months. The primary endpoint was complete clinical response (CCR) at 6 months after local imiquimod treatment or one surgical intervention. Primary analysis was per protocol with a non-inferiority margin of 20%. This trial is registered at ClinicalTrials.gov, NCT01861535. 110 patients with vHSIL (78% with unifocal vHSIL and 22% with multifocal vHSIL) were randomly assigned between June 7, 2013, and Jan 8, 2020. Clinical response to treatment could be assessed in 107 patients (54 in the imiquimod group and 53 in the surgery group), and 98 patients (46 in the imiquimod group and 52 in the surgery group) completed the study per protocol. 37 (80%) of 46 patients using imiquimod had CCR, compared with 41 (79%) of 52 patients after one surgical intervention, showing non-inferiority of the new treatment (difference in proportion -0·016, 95% CI -0·15 to -0·18; p=0·0056). Invasive disease was found in five patients at primary or secondary surgery, but not in patients with per-protocol imiquimod treatment. There was no significant difference in HPV clearance, adverse events, and treatment satisfaction between study groups. Imiquimod is a safe, effective, and well accepted alternative to surgery for women with vHSIL and can be considered as first-line treatment. Austrian Science Fund and Austrian Gynaecological Oncology group.

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

AbstractLangerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

Rosai\u2013Dorfman\u2013Destombes disease of the nervous system: a systematic literature review

BackgroundRosai–Dorfman–Destombes disease (RDD) is a rare histiocytic disorder with heterogeneous clinical manifestations and rare neurologic involvement. The existing clinical literature about neurologic RDD has yet to be critically examined.MethodsWe performed a four-database English-language systematic literature search for cases of RDD neurohistiocytosis, excluding secondary literature. Individual patient data for neurologic symptoms, disease sites, treatments, and responses were captured. Responses to first-line and second-line surgical interventions, post-surgical radiotherapy, and systemic therapies were analyzed.ResultsAmong 4769 articles yielded by literature search, 154 articles were fully reviewed, containing data on 224 patients with neurologic RDD. 128 (83.1%) articles were single case reports. 149 (66.5%) patients were male, 74 (33.5%) female, with a median age of 37.6 years (range 2–79). Presenting neurologic symptoms included headache (45.1%), focal neurological deficits (32.6%), visual symptoms (32.1%), and seizures (24.6%). RDD involvement was multifocal in 32 (14.3%) cases. First-line treatment involved resection in 200 (89.6%) patients, with subsequent progression in 52 (26%), including 41 (78.8%) with unifocal disease. No difference was observed in progression-free survival comparing post-operative radiotherapy to no radiotherapy following partial resection. Chemotherapy given alone as first-line treatment led to complete or partial response in 3/7(43%) patients. Second-line treatments led to complete or partial response in 18/37(37.5%) patients. Mutational data were reported on 10 patients (4.46%).ConclusionsThis review highlights the limited published data about neurologic RDD, which presents with varied symptomatology and outcome. Further study is needed about its mutational landscape, and more effective therapies are needed for recurrent and refractory disease.

Do prostate MRI reports consider focal therapy when describing diagnostic findings? A descriptive review and analysis of concordance among prostate MRI reports and radical prostatectomy pathology reports.

41 Background: Focal therapy (FT) for prostate cancer (PCa) is becoming an attractive option for men seeking treatments that minimize the morbidity of whole gland therapy. Prostate MRI reports should include lesion location, presence of bilateral extension and presence of multifocality as these radiographic features are essential in selecting appropriate candidacy. We aim to evaluate concordance of disease between MRI and final pathology reports. Methods: We conducted a retrospective review of pathology reports from radical prostatectomies (RP) performed at our institution between 2016-2019, in patients whom also underwent pre-operative prostate MRI’s. The number and locations of PI-RADS ≥ 3 lesions described in MRI reports were compared against the RP findings and assessed for disease concordance in terms of lesion location, extent (unilateral vs. bilateral extent) and/or the presence of tumor multifocality. Fischer’s exact test was used for statistical analysis. Results: A total of 1593 patients underwent RP, among which 416 (26.1%) had preoperative prostate MRI’s. A majority (65.3%) (n = 273/416) of MRI’s reported a single PI-RADS &gt; 3 lesion, 51/416 (12.3%) had negative MRI’s and 22.1% (92/416) described &gt;2 PI-RADS ≥ 3 lesions. A total of n = 388/416 (93.2%) had detailed descriptions of their MRI and path reports for comparative analysis. MRI and final path tumor concordance with respect to unifocal extent or multifocality was low at 37.2%. When a single PI-RADS &gt; 3 lesion was described, concordance with final path was 37.6% as compared to 55.6% when &gt;2 lesions were described (p = 0.006). Discordant findings at final path included the presence of tumor multifocality (80.7%) or the extent of a unifocal lesion (19.3%). Lesions crossing the midline were uncommonly reported on MRI (16%). When prostate midline assessment was included in the evaluation of lesion extent, the degree of concordance with final pathology improved from 33.3% to 64.2% (p = 0.038). Conclusions: Prostate MRI reports have a large discordance with RP reports. Tumor multifocality and/or unifocal disease crossing the midline may not hold significant meaning if the disease is ultimately organ confined and the treatment is aimed at the whole gland. However, in the context of focal therapy, these findings are of germane importance. Radiologists are encouraged to consider focal therapy as a treatment strategy when describing MRI findings and acknowledge the importance of tumor multifocality/bilaterality in this context.

Abstract P4-09-02: The impact of breast conserving surgery re-excision on patient-reported outcomes using the BREAST-Q

Abstract Introduction: Although SSO/ASTRO consensus margin guidelines have led to decrease rate of re-excision, some women require additional surgery. Re-excision surgery may cause psychosocial stress and impact cosmetic outcomes and breast satisfaction. The purpose of this study was to assess patient-reported outcomes using the BREAST-Q breast satisfaction, psychosocial wellbeing, and sexual wellbeing subscales for women with breast cancer following index breast-conserving surgery (BCS). Methods: Women with stage 0 to 3 breast cancer undergoing BCS who completed a BREAST-Q from 2010 to 2016 were identified by retrospective review of a prospective database. The BREAST-Q breast conserving therapy module was used to assess outcomes between women with 1 BCS and those with ≥1 re-excision surgery (R-BCS). Baseline characteristics were compared, and linear mixed models were used to analyze associations with BREAST-Q scores over time. Results: Our study group was initially composed of 2570 women that was narrowed to 2549 women after excluding 21 who ultimately underwent mastectomy; 1982 (78%) had 1 BCS and 567 (22%) had ≥1 R-BCS. The median age of the cohort was 57 years (range 26-97). Women with 1 BCS were more likely to be older (p&amp;lt;0.001), have a higher BMI (p=0.01), present with invasive carcinoma (p=0.03), have unifocal disease (p&amp;lt;0.001), undergo surgery post-release of SSO Invasive Guidelines (p&amp;lt;0.001), receive endocrine therapy (p=0.006), and less likely to receive radiation therapy (p=0.02) compared to those with ≥1 R-BCS. At 2-years post-operative, women with ≥1 R-BCS compared to 1 BCS were noted to have lower average breast satisfaction and sexual well-being scores (76.0 vs. 71.8 [p=0.03] and 70.2 vs. 64.0 [p=0.01], respectively). No difference in psychosocial well-being scores existed for up to 5 years of post-operative follow-up. Multivariable linear regression confirmed that undergoing ≥1. R-BCS is a risk factor for decreased breast satisfaction and sexual well-being at 2 years postoperative. On multivariable analysis, re-excision was found to be associated with lower breast satisfaction and sexual well-being scores. (p=0.01 and p=0.02, respectively), while it was not associated with a change in psychosocial wellbeing score (p=0.07). Factors such as Race, BMI, and marital status were not associated with any difference across all subscales (all p&amp;gt;0.1). Chemotherapy and radiotherapy were associated with lower scores across all subscales (Table). Younger age was associated with lower psychosocial and sexual well-being scores (both p&amp;lt;0.001), and endocrine therapy was associated with a lower sexual well-being score (p=0.01). Conclusions: Psychosocial well-being in women with 1 BCS for breast cancer were largely comparable over time to those who underwent ≥1 R-BCS. At 2 years post-operative, women with 1-BCS had lower breast satisfaction and sexual well-being, but this difference did not remain at later time periods. These findings may help in counseling women who are concerned of satisfaction and quality of life outcomes with BCS if breast re-excision was necessary. Multivariable analysis of BREAST-Q Subscale scoresEstimateStandard Errorp valueBreast SatisfactionAge at surgery-0.0690.0480.147BMI-0.1380.0810.088Chemotherapy-2.5421.0260.015Adjuvant radiation-3.4371.5830.031Hormonal therapy-0.6511.1700.119≥1 R-BCS vs. 1 BCS-2.5420.8840.008Psychosocial well-beingAge at surgery0.1980.043&amp;lt;0.001BMI-0.079-0.0790.287 Chemotherapy-3.2090.9330.001Adjuvant radiation-4.5091.4600.004Hormonal therapy0.2081.0740.528≥1 R-BCS vs. 1 BCS-1.4450.7930.059Sexual well-beingAge at surgery0.2700.072&amp;lt;0.001BMI-0.1140.1180.337Chemotherapy-4.7131.428&amp;lt;0.001Adjuvant radiation-7.6292.493&amp;lt;0.001Hormonal therapy-1.1801.7080.008≥1 R-BCS vs. 1 BCS-2.9661.2190.015 Citation Format: Regina Matar, Meghan Flanagan, Sarah Fuzesi, Kathyrn Haglich, Shen Yin, Varadan Sevilimedu, Jonas Nelson, Mary L. Gemignani. The impact of breast conserving surgery re-excision on patient-reported outcomes using the BREAST-Q [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-09-02.

Adult Langerhans Cell Histiocytosis and the Skeleton.

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia in which somatic mutations in components of the MAPK/ERK pathway have been identified. Osseous involvement is evident in approximately 80% of all patients and may present as a single osteolytic lesion, as a multi-ostotic single system disease or as part of multisystem disease. Both exogenous, such as treatment with glucocorticoids, and endogenous parameters, such as anterior pituitary hormone deficiencies and inflammatory cytokines, may severely affect bone metabolism in LCH. Computed tomography (CT) or magnetic resonance imaging (MRI) are usually required to precisely assess the degree of bone involvement; 18F-fluorodeoxyglucose (FDG) positron emission tomography—CT can both detect otherwise undetectable LCH lesions and differentiate metabolically active from inactive or resolved disease, while concomitantly being useful in the assessment of treatment response. Treatment of skeletal involvement may vary depending on location, extent, size, and symptoms of the disease from close observation and follow-up in unifocal single-system disease to chemotherapy and gene-targeted treatment in cases with multisystem involvement. In any case of osseous involvement, bisphosphonates might be considered as a treatment option especially if pain relief is urgently needed. Finally, a patient-specific approach is suggested to avoid unnecessary extensive surgical interventions and/or medical overtreatment.

Chronic recurrent multifocal osteomyelitis: A multidisciplinary experience of 22 pediatric cases with a mean follow-up of 27 months

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is not a well known disorder among nonpediatricians. The aim of this study is to retrospectively evaluate the clinical outcomes of twenty-two CRMO patients presenting to two referral centres. MethodsThis retrospective study included twenty-two children (12 males, 10 females; mean age 13 years; range 7–17 years). The diagnosis was based on clinical, radiological, and pathological findings. Data were retrieved from hospital charts. ResultsThe mean delay in diagnosis was 26 months (range, 0–96 months). The mean follow-up after diagnosis was 27.4 months (range, 6–47 months). Symptoms included pain, limping, local swelling, morning stiffness, and fever. 18 patients had multifocal and 4 patients had unifocal disease. Bone lesions were detected with whole-body or local MRI (Magnetic Resonance Imaging). The mean number of bone lesions was 2.5 (range, 1–8). Ten cases underwent biopsy to exclude malignancy and infection. Prior to diagnosis, cast immobilization or curettage was erroneously performed in four patients. One patient suffered from vertebral compression fracture. There is no growth disturbance or deformity in any patient. ConclusionThis study demonstrated that early recognition of the disease can be improved by using Bristol criteria which should be evaluated by a multidisciplinary team rather than one single specialist. In this way, the reliability of these criteria is improved and the treatment could be given earlier with decreased delay in diagnosis. This multidisciplinary approach is also important for decision for biopsy, timely aggressive medical treatment, and follow-up of the disease to minimise possible complications.

Impact of Multifocality on the Recurrence of Papillary Thyroid Carcinoma.

The incidence of thyroid cancer has dramatically increased over the last few decades, and up to 60% of patients have multifocal tumors. However, the prognostic impact of multifocality in patients with papillary thyroid carcinoma (PTC) remains unestablished and controversial. We evaluate whether multifocality can predict the recurrence of PTC. A total of 1249 patients who underwent total thyroidectomy for PTC at the Ewha Medical Center between March 2012 and December 2019 were reviewed. In this study, multifocality was found in 487 patients (39.0%) and the mean follow-up period was 5.5 ± 2.7 years. Multifocality was associated with high-risk features for recurrence, including extrathyroidal extension, lymph node metastasis, and margin involvement. After adjustment of those clinicopathological features, 10-year disease-free survival was 93.3% in patients with multifocal tumors, whereas those with unifocal disease showed 97.6% (p = 0.011). Multivariate Cox regression analysis indicated that male sex (HR 2.185, 95% CI 1.047–4.559), tumor size (HR 1.806, 95% CI 1.337–2.441), N1b LN metastasis (HR 3.603, 95% CI 1.207–10.757), and multifocality (HR 1.986, 95% CI 1.015–3.888) were independent predictors of recurrence. In conclusion, multifocality increased the risk of recurrence in patients with PTC. Patients with multifocal PTCs may need judicious treatment and follow-up approaches.

Multifocal regression and pathologic response predicts recurrence after neoadjuvant chemotherapy in head and neck squamous cell carcinoma

ObjectivesComplete pathological response after neoadjuvant chemotherapy (NAC) in head and neck squamous cell carcinomas (HNSCC) is a good prognostic factor. Multifocal regression post-NAC in breast cancer has proven to impact locoregional control (LRC) but has not been evaluated in HNSCC. We evaluate the impact of multifocal regression and major pathologic response (MPR) on survival indices in HNSCC. Materials and MethodsRetrospective review of HNSCC patients receiving NAC followed by surgery with curative intent between March 2016 to March 2019 at MD Anderson Cancer Center. Tumor focality (uni- or multifocal), pathologic response and other pathologic data were collected. MPR was defined as ≤ 10% residual tumor. Overall survival (OS) and LRC were analyzed and multivariate Cox regression analysis was performed. Results101 patients were analyzed, with 18.8% pathologic complete response, 18.8% with 1–10% viable tumor and 60.4% with > 10% viable tumor. 61 (60.4%) had unifocal disease while 19 (18.8%) had multifocal disease. Tumor focality was significantly associated with LRC but not OS, where the 3-year LRC was 82%, 69% and 52% (p = 0.015) for no viable tumor, unifocal disease and multifocal disease respectively. On multivariate analysis, multifocal disease (HR 10.43; 95 %CI 1.24–87.5) and extranodal extension (HR 4.4; 95 %CI 1.60–12.07) continued to be significant independent predictors of LRC. MPR group displayed significantly better 3-year OS (75% vs 51%, p = 0.041) and 3-year LRC (80% vs 62%, p = 0.011) than those with > 10% viable tumor. ConclusionMultifocal regression and less than MPR after NAC in HNSCC predicts for locoregional recurrence and should be routinely reported.

A UK based two-centre review of multifocality and its role in the treatment of papillary thyroid cancer

IntroductionMultifocality is increasingly observed in papillary thyroid carcinoma (PTC) due to improvements in imaging and histopathological analysis. However, its significance in management, particularly as a sole risk-factor, remains controversial. This study aimed to investigate the prognostic value of multifocality in predicting recurrence following thyroid lobectomy in a contemporary group of PTC patients managed in the UK. MethodsPatients with PTC in NHS Lothian (2009-19) and Guys and St Thomas NHS Foundation Trust (2012-19) were identified. Categorical variables were compared using Chi-squared or Fisher's exact test. Five-year recurrence free survival (RFS) were analysed using Kaplan-Meier method and compared using log-rank. ResultsOf 828 patients; 492 (59%) had unifocal and 336 (41%) multifocal disease on final pathology. A higher rate of pathological nodal disease (22%v36%,p < 0.001), total thyroidectomy (TT) (78%v92%,p < 0.001) and radioactive iodine (RAI) (57%v75%,p < 0.001) was demonstrated in patients with multifocality. With a median follow-up of 50 months, overall 5-year RFS was 96.5%; 96.5% for unifocal versus 96.6% for multifocal disease (p = 0.695). Recurrence was not shown to be associated with multifocality on either univariate or multivariate analysis. Amongst patients with T1/2N0M0 disease (n = 341), more patients were treated with TT and RAI with multifocal compared to unifocal disease (<0.001). Only two patients within this group recurred during follow up, both of whom had multifocal disease and were treated with TT and RAI (5yRFS100%v98.1%,p = 0.051). ConclusionMultifocality is a common feature of PTC but does not appear to be an independent predictor of outcome. Therefore, treatment intensification on the basis of multifocality alone seems unwarranted.

Long-Term Outcomes Using Electron IOERT APBI for Early Stage Breast Cancer: The Verona University Hospital Experience

From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status. With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively. Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.