Adjuvant Radio Research Articles

Telehealth weight loss program for breast cancer survivors is feasible and acceptable: Preliminary results of pilot clinical trial.

TPS1603 Background: Current weight loss programs for breast cancer survivors utilize a hybrid of in-person visits or individualized telephone-based sessions modeled after the Diabetes Prevention Program. Telehealth may be an effective and efficient means of communicating with patients who otherwise cannot participate in in-person visits. To test this concept, we conducted a pilot single-arm study (NCT04855552) to examine the feasibility and acceptability of a weight loss group program via telehealth for breast cancer survivors. Methods: Patients > = 18 years with ECOG performance 0 or 1, a BMI of ³ 25 kg/m2, and completion of adjuvant radio- and/or chemo-therapy > 6 months were eligible. Patients attended weekly zoom teleconference counseling grouped sessions either at noon or 5 pm led by a licensed clinical psychologist for 20 weeks followed by sessions in weeks 22 and 24. Patients were encouraged to use MyFitnessPal.com, an online tool, to monitor calorie intake and physical activity and digital scales to monitor weight to share with study staff to enhance accountability and provide opportunity for feedback. Feasibility was defined as a ratio of enrolled/eligible patients ≥50%. Acceptability was assessed from surveys pre- and post-treatment, and qualitatively from exit interviews. Secondary endpoints included changes in Quality of Life-Breast Cancer Patient (QOF-BC), Patient Health Questionnaire (PHQ-9), and percent weight loss from baseline to 24 weeks. Results: Clinical characteristics of patients are summarized in Table. The ratio of enrolled (n = 12)/eligible (n = 23) participants was 52% thus confirming study feasibility. One patient dropped out after 2 sessions. Qualitative results from exit interviews showed that 7/9 patients rated the telehealth format as “extremely acceptable”. Surveys also indicated that the format and delivery of the program remained acceptable across most domains with no significant changes, except an increase in “approval” from 4.1 to 4.7 ( p= 0.05). Patients’ mood improved on the PHQ-9 from 4.2 to 1.2 (p = 0.03), and QOL-Physical Wellbeing improved from 56.9 to 66.3 (p = 0.004). Overall, 199 of 236 participant-sessions (84%) were attended. Percent weight loss was 6.5% +/- 2.5%. Conclusion: This proof-of-concept weight loss program was feasible and acceptable for our patients yielding improvements in QOL, mood, and a clinically significant weight loss over 6-months. This group-based video approach represents an intervention strategy that could be widely-disseminated and may provide stronger accountability/support than a one-on-one approach in some patients. Future work is aimed at refining strategies to increase patient enrollment/retention. Clinical trial information: NCT04855552. [Table: see text]

Combined interdisciplinary treatment of metastatic bone lesions – embolization, biopsy, ablation, and surgery in one operative sitting

Abstract Objective As a result of modern cancer treatment and thereby improved survival, many cancers spread to bone. Bone metastases may cause immobilizing pain and increase the risk of fracture even by inadequate or no trauma. Treatment of these patients should promptly address confirmation of the tumor entity, local control as well as adequate and lasting surgical stabilisation of the affected bone or joint. We present a setup to perform all the above in a single operative sitting. Methods Required imaging is completed before initial consultation. The treatment plan is discussed in an interdisciplinary team according to the primary tumor and thereof resulting survival estimation, the imaging evaluation and patient's expectations and needs. In a single operative setup, the patients are treated by an interventional radiologist and an orthopaedic surgeon in a hybrid operating room. Thus, in one single setup the patient may undergo arteriogram to diagnose hypervascularity of the tumor followed by embolization if needed, CT-guided biopsy, percutaneous radiofrequency or cryotherapy ablation of the metastases for local tumor control and eventually surgical treatment with resection of the tumor, joint replacement or minimally-invasive stabilization as needed. Biopsy results may be discussed at inhouse tumor boards and adjuvant radio- or chemotherapy may be planned for the postoperative course. Results Five combined procedures were performed in 5 patients (3 female, 2 male patients; median age 65 years (range 61–77)) each in one single operative sitting since October 2021. Three patients suffered from metastases of renal cell carcinoma, one each from thyroid carcinoma and breast cancer respectively. Metastases were located in the femoral meta- and diaphysis in 3 cases and in the acetabulum in 2 cases. Median duration of this multidisciplinary intervention was 375 min (251–426). Median length of hospital stay was 5 days (3–10). Median time from referral to definitive treatment was 24 days (17–32). All patients were able to walk with crutches immediately after treatment. No complications occurred. Conclusion Combined multidisciplinary treatment of patients with metastatic bone disease is possible and may be favourable in respect of minimising the number of consultations, anaesthesias and interventions. This should lead to accelerated and pain-free mobilisation, thus maximising the patients’ quality of life.

The Prognostic Significance of p16 and its Role as a Surrogate Marker for Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Analysis of 281 Cases.

This study analyzed the expression of p16 in a large cohort of patients suffering from oral squamous cell carcinoma (OSCC) who received initial surgical therapy in order to evaluate the prognostic significance of p16 expression and to analyze its value as a surrogate marker to determine human papilloma virus (HPV) status. Immunohistochemical staining of p16 was performed on tissue microarrays. Different expression levels of p16 (>25%; >50%; ≥70%) with a moderate to strong intensity were correlated with the clinical outcome. HPV DNA was analyzed by polymerase chain reaction (PCR). A total of 281 patients were included in this study. The p16 expression obtained using the abovementioned three different cutoffs did not significantly influence 5-year overall survival (OS) (p=0.23; p=0.45; p=0.23) nor recurrence-free survival (RFS) (p=0.79; p=0.45; p=0.142). In univariate Cox regression analysis, the p16 expression level was not a risk factor for OS (HR=0.637; 95%CI=0.271-1.5; p=0.300) and RFS (HR=0.74; 95%CI=0.339-1.61; p=0.449). A total of 17 patients (6.0%) were p16 positive with a cutoff ≥70%. HPV DNA was found in 4/11 of these cases by PCR, resulting in a positive predictive value of 0.36. In patients receiving adjuvant radio(chemo)therapy, a significantly (p=0.042) longer OS was observed in patients with p16 expression greater than 25% vs. ≤25%. In comparison with OPSCC, (strong) p16 positivity is rare in OSCC; however, in patients receiving primary surgery with adjuvant radio(chemo)therapy, p16 expression is associated with a higher survival rate. In conjunction with prior studies, p16 does not seem to be a reliable surrogate marker for HPV infection in OSCC.

The phenotypical features and risk factors for progression of endometrial stromal tumors

Endometrial stromal sarcomas are mesenchymal tumors and constitute 0,2-1% of all the malignant uterine pathologies and 6-20% of uterine sarcomas. Commonly they arise in 42-53 year old women. Unlike epithelial tumors, that are having better prognosis, uterine sarcomas are known to have bad prognosis. The recurrence rate and the risk of distant metastasis is high. Local recurrence can be even seen 20-30 years after primary diagnosis and therapy. Radical surgery stands as the primary therapeutic method, often with adjuvant radio- and chemotherapy. Due to the low incidence of endometrial stromal sarcomas, only few things are known about the risk factors of bad outcome and its optimal management.

Tissue Microarray Analyses Suggest Axl as a Predictive Biomarker in HPV-Negative Head and Neck Cancer

Simple SummaryDespite many efforts, no predictive biomarkers that could guide clinical decision making and personalized treatment have been established for patients with head and neck squamous cell carcinoma. We propose that high expression of the tyrosine kinase receptor Axl identifies patients as being at enhanced risk for treatment failure under surgery alone and, hence, should be treated by primary or adjuvant radiotherapy.The receptor tyrosine kinase Axl is described to promote migration, metastasis and resistance against molecular targeting, radiotherapy, and chemotherapy in various tumor entities, including head and neck squamous cell carcinoma (HNSCC). Since clinical data on Axl and its ligand Gas6 in HNSCC are sparse, we assessed the association of Axl and Gas6 expression with patient survival in a single center retrospective cohort in a tissue microarray format. Expression was evaluated manually using an established algorithm and correlated with clinicopathological parameters and patient survival. A number of 362 samples yielded interpretable staining, which did not correlate with T- and N-stage. Protein expression levels were not associated with the survival of patients with p16-positive oropharyngeal SCC. In HPV-negative tumors, Axl expression did not impact patients treated with primary or adjuvant radio(chemo)therapy, but was significantly associated with inferior overall and recurrence-free survival in patients treated with surgery alone. Gas6 was a positive predictor of survival in patients whose treatment included radiotherapy. Associations remained significant in multivariable analysis. Our data question a meaningful contribution of the Axl/Gas6 pathway to radio-resistance in HNSCC and instead suggest that strong Axl expression identifies tumors requiring adjuvant radio(chemo)therapy after surgery.

Outcome and risk factors for local recurrence after breast conserving surgery in patients affected by ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a tumor with long term survival and low local recurrence rate. Although the progression of these lesions is rare, the current guidelines recommend breast conservating surgery (BCS) with adjuvant radio and/or endocrine therapy, often resulting in an overtreatment for patients. The aim of this single-center study was to evaluate the long-term outcome of the breast conservating surgery of DCIS followed by adjuvant radio and/or endocrine therapy and to identify prognostic factors associated with the risk of recurrence. Patients treated for DCIS with BCS and radiation therapy between March 2006 and January 2019 were retrospectively reviewed using a prospectively maintained database. Analysis of the potential risk factors was performed to evaluate the risk of subsequent ipsilateral and contralateral recurrence. Out of 2894 patients, two hundred eighty-eight (10%) patients were treated for DCIS. After a median follow-up of 85 months (IQR 27-124), the incidence of recurrence was 6% (18 patients). Nine of them (3%) had an ipsilateral local recurrence (LR) with a median disease-free survival of 19 months (IQR 12-35). The remaining nine patients had contralateral metachronous breast cancer (CBC) with a median DFS of 29 months (IQR 14-36). Margin status, multifocality, hormone receptor status and Her-2/Basal-like subtype were identified as risk factors for the local recurrence with a OR of 5.58 (1.44-21.54), 7.46(1.89-24.48) 0.25 (0.06-0.96) and 4.86 (1.26-18.71) respectively. DCIS had been confirmed to have long term survival. Margin status, multifocality, hormone receptor status and Her-2/Basal-like subtype could be identified as reliable risk factors for the progression of the disease.

Anaplastic pleomorphic xanthoastrocytoma - single-center analysis of 42 patients

To study neuroimaging, morphological features of tumors, as well as factors affecting treatment and prognosis. A retrospective study enrolled 42 patients operated on at the Burdenko Neurosurgery Center between 2003 and 2020. MR characteristics of anaplastic pleomorphic xanthoastrocytoma were analyzed. All patients underwent resection of tumor (total resection in 83.3% of cases). Redo surgeries were performed in 1/3 of patients. Mutational status of BRAF V600E was assessed in all patients. Adjuvant radio- and chemotherapy was performed in more than 80% of cases. Tyrosine kinase inhibitors were administered in 19% of cases. The follow-up period was 152 months (median 34 months). We found no pathognomonic MR signs of this disease. Indeed, anaplastic pleomorphic xanthoastrocytoma have the same signal characteristics as other malignant gliomas. The BRAF V600E mutation status was positive in 54.8% of cases. None patient had IDH-1 mutation. Mean Ki-67 index was 12.5%. The overall survival was 79 months (range 4-152). Seven (17%) patients are alive for more than 90 months. Only Ki-67 index and BRAF mutation significantly influenced the treatment prognosis and overall survival regardless the use of tyrosine kinase inhibitors. Such well-known factors for malignant glioma as patient age, total resection and adjuvant therapy did not significantly affect overall survival. Perhaps, searching for new molecular genetic features will reveal additional significant factors of prognosis in patients with anaplastic pleomorphic xanthoastrocytoma.

Myxofibrosarcoma landscape: diagnostic pitfalls, clinical management and future perspectives.

Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a predilection of the extremities and a high local recurrence rate. Originally classified as a myxoid variant of malignant fibrous histiocytoma, this musculoskeletal tumor has been recognized since 2002 as a distinct histotype showing a spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels. Currently, the molecular pathogenesis of MFS is still poorly understood and its genomic profile exhibits a complex karyotype with a number of aberrations including amplifications, deletions and loss of function. The diagnosis is challenging due to the unavailability of specific immunohistochemical markers and is based on the analysis of cytomorphologic features. The mainstay of treatment for localized disease is represented by surgical resection, with (neo)-adjuvant radio- and chemotherapy. In the metastatic setting, chemotherapy represents the backbone of treatments, however its role is still controversial and the outcome is very poor. Recent advent of genomic profiling, targeted therapies and larger enrollment of patients in translational and clinical studies, have improved the understanding of biological behavior and clinical outcome of such a disease. This review will provide an overview of current diagnostic pitfalls and clinical management of MFS. Finally, a look at future directions will be discussed.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP)

IntroductionIn contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives.Material and methodsBetween January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval.ResultsDepending on the median time interval of 55 days (d) (95% CI 51.42–84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%).Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months).The 5-year OS rate for all patients involved was 71% (95% CI 0.55–0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48–1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42–0.80; X2(1) = 1.16, p = 0.281).Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75–0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89–1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57–0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59–0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63–0.94) and thus not significantly different from 65% (95% CI 0.45–0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589).ConclusionsThe results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

NCOG-25. REVISITING THE PIGNATTI RISK SCORE IN LOW-GRADE GLIOMA PATIENTS IN THE MOLECULAR ERA

Abstract Until now, the Pignatti risk score has been used to guide treatment decisions after histological diagnosis of diffuse glioma WHO grade 2. However, its prognostic value was derived from a historic cohort that has been diagnosed by morphologic rather than molecular criteria. We re-challenged the Pignatti score in a contemporary, molecularly characterized cohort. From our institutional cohort of 422 diffuse gliomas WHO grade 2, 202 patients were identified for whom IDH mutation status was known and 1p/19q co-deletion or loss of ATRX expression unambiguously classified tumors into astrocytoma or oligodendroglioma. Patients with IDH wildtype astrocytoma (n=9), multifocal lesions or brainstem involvement were excluded. Potential prognostic factors including the individual items of the Pignatti score (astrocytoma; age ≥40 years; neurologic deficit; maximum tumor diameter ≥6cm; tumor crossing midline) were correlated with progression-free survival (PFS) by univariate log-rank und multivariate Cox regression analysis. 165 patients with astrocytoma or oligodendroglioma were analysed of whom 109 (66%) did not receive adjuvant radio- or chemotherapy. 94 untreated patients with a minimum follow-up of 24 months entered survival analysis. These patients were classified as “high-risk” (Pignatti 3-5) and “low-risk” (Pignatti 0-2) in 15% and 85% and did not differ with regard to potential prognostic factors (gender; resection vs. biopsy; tumor recurrence) other than the individual Pignatti score items. Diameter ≥6 cm (p=0.006; HR=2.18) and midline crossing (p=0.003; HR=3.54) were identified as independent prognostic factors of PFS. Noteworthy, prognostic factors coincided when all patients (n=144) with a minimum follow-up of 24 months, regardless of adjuvant treatment, were analysed. In IDH mutant, molecularly characterized diffuse gliomas WHO grade 2, the Pignatti risk score as a whole no longer seems to be of prognostic relevance. Instead, outcome seems to be determined by tumor burden.

Reduced diffusion in white matter after radiotherapy with photons and protons

Background and purposeRadio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation. Materials and methods70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions. ResultsWe observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: −7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly. ConclusionsIrradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass.

Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV). Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival (p = 0.946) or OS (p = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached. Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B, BMI-1, and CD44 in Different Tissues of HNSCC Patients.

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues.

Malignant Sinonasal Tumors: Update on Histological and Clinical Management.

Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4–9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.

Abstract 553: Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study

Abstract Introduction Head and neck squamous cell carcinoma (HNSCC) remains a substantial burden to global health. Despite evolving therapies, 5-year survival is less than 50% and unlike other cancers, reliable biomarkers to monitor treatment response do not exist. Cell-free circulating tumor DNA (ctDNA) is an emerging biomarker but has not yet been studied sufficiently for HNSCC. The detection of ctDNA as a marker of minimal residual disease following curative-intent treatment holds promise for identifying patients at an increased risk of relapse, who may benefit from adjuvant radio(chemo)therapy or facilitate close monitoring with repeat resection if needed. Methods We conducted a single-center prospective experimental evidence-generating cohort study to assess ctDNA in 30 patients with p16-negative HNSCC (stages I-IVB) who received primary surgical treatment with curative intent at our institution. Whole exome sequencing (WES) was performed on formalin-fixed paraffin-embedded tumor tissue to a median depth of 250x. For each patient, we selected up to 48 somatic variants for personalized ctDNA assay design. We used the RaDaRTM assay to analyze serial pre- and post-operative plasma samples (range 2-6) for evidence of minimal residual disease or recurrence. Results In a subset of patients analyzed to evaluate the performance of RaDaR, personalized panels were designed with between 34 and 48 somatic variants (median 48). Preliminary data shows 100% ctDNA detection in baseline samples taken prior to surgery at tumor fractions ranging from 312 ppm (equivalent to 0.03% AF) to 7579 ppm (equivalent to 0.76% AF). In post-surgery samples, ctDNA could be detected at levels as low as 26 ppm (equivalent to 0.0026% AF). Analysis of follow-up plasma samples will be presented along with data from the full patient cohort. Conclusions This study illustrates the potential of ctDNA as a biomarker in HNSCC and demonstrates the feasibility of personalized ctDNA assays for the detection of minimal residual disease post-treatment and for monitoring for early detection of relapse. Citation Format: Susanne Flach, Karen Howarth, Sophie Hackinger, Christodoulos Pipinikas, Kirsten McLay, Giovanni Marsico, Christoph Walz, Olivier Gires, Martin Canis, Philipp Baumeister. Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 553.

RECURRENT MALIGNANT APOCRINE SWEAT GLAND CARCINOMA - A CASE REPORT

Apocrine carcinomas arise from normal or modified sweat glands. The slow-growing nature and rarity of sweat gland carcinomas complicate their diagnosis at the early stage. The incidence of PASGC is quite low at 0.0049–0.0173 cases/100,000 persons/year. A 21-year-old male patient was presented in February 2016 with small solitary mass in the right axilla with mild tenderness and pain. Underwent wide local excision and axillary dissection at our institution followed by adjuvant radio and chemotherapy. Later on, after 18 months developed local recurrence and was planned for re-surgery and a second phase of palliative radiotherapy. After a year, presented to the hospital with pin sized irregular swelling in the axilla. Sweat gland carcinomas which are rarely diagnosed create a pathological dilemma due to their unpredicted biological behavior. However, wide local excision with or without nodal dissection is the primary treatment till date. In this particular case even though patient had underwent axillary node dissection, patient had recurrence twice with no distant metastasis which is a key point to be noted. Thorough study of the available apocrine carcinoma case reports or case series, the better knowledge regarding the apocrine carcinoma can be obtained.

What Is the Implant Survivorship and Functional Outcome After Total Humeral Replacement in Patients with Primary Bone Tumors?

Total humeral replacement is an option to reconstruct massive bone defects after resection of locally advanced bone tumors of the humerus. However, implant survivorship, potential risk factors for implant revision surgery, and functional results of total humeral replacement are poorly elucidated because of the rarity of the procedure. We asked: (1) What is the revision-free implant and overall limb survivorship after total humerus replacement? (2) What factors are associated with implant revision surgery? (3) What is the functional outcome of the procedure as determined by the Musculoskeletal Tumor Society (MSTS) score and the American Shoulder and Elbow Surgeons (ASES) score? Between August 1999 and December 2018, 666 patients underwent megaprosthetic reconstruction after resection of a primary malignant or locally aggressive/rarely metastasizing tumor of the long bones at our department. In all, 23% (154) of these patients had a primary tumor located in the humerus. During the study, we performed total humeral replacement in all patients with a locally advanced sarcoma, in patients with pathological fractures, in patients with skip metastases, or in patients with previous intralesional contaminating surgery, who would have no sufficient bone stock for a stable implant fixation for a single joint megaprosthetic replacement of the proximal or distal humerus. We performed no biological reconstructions or reconstructions with allograft-prosthetic composites. As a result, 5% (33 of 666) of patients underwent total humerus replacement. Six percent (2 of 33) of patients were excluded because they received a custom-made, three-dimensionally (3-D) printed hemiprosthesis, leaving 5% (31) of the initial 666 patients for inclusion in our retrospective analysis. Of these, 6% (2 of 31) had surgery more than 5 years ago, but they had not been seen in the last 5 years. Median (interquartile range) age at the time of surgery was 15 years (14 to 25 years), and indications for total humeral replacement were primary malignant bone tumors (n = 30) and a recurring, rarely metastasizing bone tumor (n = 1). All megaprosthetic reconstructions were performed with a single modular system. The implanted prostheses were silver-coated beginning in 2006, and beginning in 2010, a reverse proximal humerus component was used when appropriate. We analyzed endoprosthetic complications descriptively and assessed the functional outcome of all surviving patients who did not undergo secondary amputation using the 1993 MSTS score and the ASES score. The median (IQR) follow-up in all survivors was 75 months (50 to 122 months), with a minimum follow-up period of 25 months. We evaluated the following factors for possible association with implant revision surgery: age, BMI, reconstruction length, duration of surgery, extraarticular resection, pathological fracture, previous intralesional surgery, (neo-)adjuvant radio- and chemotherapy, and metastatic disease. The revision-free implant survivorship at 1 year was 77% (95% confidence interval 58% to 89%) and 74% (95% CI 55% to 86%) at 5 years. The overall limb survivorship was 93% (95% CI 75% to 98%) after 1 and after 5 years. We found revision-free survivorship to be lower in patients with extraarticular shoulder resection compared with intraarticular resections (50% [95% CI 21% to 74%] versus 89% [95% CI 64% to 97%]) after 5 years (subhazard ratios for extraarticular resections 4.4 [95% CI 1.2 to 16.5]; p = 0.03). With the number of patients available for our analysis, we could not detect a difference in revision-free survivorship at 5 years between patients who underwent postoperative radiotherapy (40% [95% CI 5% to 75%]) and patients who did not (81% [95% CI 60% to 92%]; p = 0.09). The median (IQR) MSTS score in 9 of 13 surviving patients after a median follow-up of 75 months (51 to 148 months) was 87% (67% to 92%), and the median ASES score was 83 (63 to 89) of 100 points, with higher scores representing better function. Total humeral replacement after resection of locally advanced bone tumors appears to be associated with a good functional outcome in patients who do not die of their tumors, which in our study was approximately one- third of those who were treated with a resection and total humerus prosthesis. However, the probability of early prosthetic revision surgery is high, especially in patients undergoing extraarticular resections, who should be counseled accordingly. Still, our results suggest that if the prosthesis survives the first year, further risk for revision appears to be low. Future studies should reexamine the effect of postoperative radiotherapy on implant survival in a larger cohort and evaluate whether the use of soft tissue coverage with plastic reconstructive surgery might decrease the risk of early revisions, especially in patients undergoing extraarticular resections. Level III, therapeutic study.

Is there a benefit for adjuvant radio(chemo)therapy in early cervical cancer? Results from a population-based study.

Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received. The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status. In low-risk patients, there was no difference in OS (p = 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (p = 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (p = 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (p = 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group-both in RCT and RT groups compared to surgery alone-the effects did not prove to be significant. Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.

Factors associated with epiphora following orbital-sparing maxillectomy via modified Weber-Ferguson incision with lower blepharoplasty.

The aims of the study were to estimate the frequency of epiphora and to identify factors associated with epiphora after orbital-sparing maxillectomy via modified Weber-Ferguson incision with lower blepharoplasty (OSOSM-MWFILB). We performed a retrospective cohort study enrolling a sample derived from the patient population undergoing OSM-MWFILB over a 7-year period. The predictor variables were grouped into demographic, related health status, anatomic, tumor-specific, and therapeutic categories. The primary outcome variable was the presence of postmaxillectomy epiphora (PME). Descriptive, univariate, and multivariate regression mixed-effect models were computed. The study sample was composed of 134 patients (46.3% females; 71.6% squamous cell carcinomas) with a mean age of 64.7 ± 12.2 years. There were 23 (17.2%) PME events, which were significantly associated with eight variables: male gender, poor general health (ASA III-IV), large vertical defect (Brown and Shaw's class III-IV), squamous cell carcinoma tumor type, big tumor size (T3-4), cervical lymph node metastasis (N1-2), long operating time > 3 h, and adjuvant radio(chemo)therapy in both univariate mixed regression and multivariate Cox hazards analyses. Healing of PME in irradiated patients was significantly delayed. Ophthalmologic consequences in patients undergoing OSM-MWFILB require particular attention, especially in case of advanced tumors, multiple comorbidities, or long surgery with postoperative radio(chemo)therapy. This emphasizes the importance of appropriate cooperation between the surgeons and ophthalmic colleagues.

The IlluminOss\xae photodynamic bone stabilization system for pathological osteolyses and fractures of the humerus: indications, advantages and limits in a series of 12 patients at 24 months of minimum follow\u2010up

BackgroundLocked titanium nails are considered the reference treatment for metastatic bone lesions of the humerus in patients with aggressive histotypes, high risk of fracture or when estimated survival is lower than 6 months.Nevertheless, they are responsible for CT and MRI artifacts which interfere with postoperative radiotherapy and follow-up.The IlluminOss® is an intramedullary stabilization system which is introduced inside the humeral canal in a deflated state, and is then distended with a monomer which hardens after exposure to blue light,stabilizing the segment; it does not cause artifacts, allowing easier and more effective radiotherapy and follow-up.The aim of this study is to report our experience, indications, possible advantages and limitations of this stabilization system at 24 months of minimum follow-up in a series of 12 patients affected by pathological fractures or impending fractures of the humerus.MethodsThis is a retrospective case-series that included all patients who underwent surgery with the IlluminOss® Photodynamic Bone Stabilization System for pathological osteolyses and fractures of the humerus. Intraoperative and postoperative complications were valued.Results12 patients and 13 procedures were included in the study. All surgeries were performed without intraoperative complications. No early postoperative complications were noted. The wounds healed in all cases and stitches were removed at two weeks from surgery, so the patients were able to perform chemotherapy after three weeks. All patients except one had a painless active range of motion which reached 90°.The VAS score was 7 preoperatively and 2.6 at one month from surgery. Pain relief was also associated to radiotherapy and chemotherapy.Unfortunately, two nail ruptures were reported at 4 and 12 months of follow-up.No artifacts were noted in the postoperative CT scans so the radiotherapy plans were easily performed without the need of dose compensation.ConclusionsThe IlluminOss® intramedullary stabilization system can provide primary stability in humeral fractures and impending fractures;the surgical technique is easy and minimally invasive.Moreover,it does not present artifacts at postoperative imaging,probably giving a better chance to perform prompt radiotherapy and chemotherapy.However, randomized clinical studies are necessary to verify its potential strength and if precocious adjuvant radio- and chemotherapy are associated to a reduction of the local progression rate.