Patients ≥ 70 years with relapsed/refractory acute myeloid leukemia (AML) have an extremely poor prognosis. we adopted a sequential therapy approach, aiming to proceed directly to allogeneic hematopoietic cell transplantation (HCT) despite active disease. We analyzed results of all consecutive patients aged over 70 years and diagnosed with primary refractory/relapsed AML who underwent HCT with sequential therapy approach (FITCy regimen) in the Aviv Sourasky Medical Center. 51 patients (median age 72 years, primary refractory, n=42/relapse, n=9). Median follow-up was 35 (range, 12-91) months. Incidences of overall and grade 3-4 acute GVHD were 39.2% (95% CI, 25.6-52.8%), and 5.9% (95% CI, 0.0-12.5%), respectively. Incidences of overall and moderate-severe chronic GVHD were 40.0% (95% CI, 25.7%-57.1%) and 29.4% (95% CI, 13.2%-46.9%), respectively. Non-relapse mortality at 3 years was 36% (95%CI 22%-49%).42/51 patients (82.4%) had CR on d+30 post HCT. Relapse incidence at 3 years was 27.8% (95% CI 14.3%-41.2%). GVHD-free relapse-free and overall survival (OS) at 3-years were 30% (95%CI 19%-47%) and 31% (95% CI 17%-55%), respectively. Multivariable analysis showed that worse ELN-2022 score, relapsed AML (vs. primary-refractory), not receiving ATG, and lower albumin prior to conditioning, were associated with higher mortality. We developed a model to predict OS that showed median OS in the low-, intermediate-, and high-risk group, not reached, 32.9 months, and 2.1 months, respectively, p

OBJECTIVE:Advancements in medulloblastoma management have improved survival; however, high-risk metastatic cases remain challenging, with approximately 60% 5-year event-free survival and significant long-term toxicity. Standard treatment includes resection of the posterior fossa tumor, followed by multimodal oncological therapy. Yet, primary tumor resection can result in treatment delay and sometimes surgical morbidity. The aim of this study was to evaluate outcomes and assess the potential of a treatment approach that includes biopsy only followed by chemotherapy and radiation therapy as a viable alternative in selected clinical scenarios. METHODS:This retrospective study included pediatric patients (age < 18 years) who were diagnosed with metastatic medulloblastoma and underwent biopsy (with or without CSF diversion) without primary tumor resection at a tertiary pediatric center between 2010 and 2023. Clinical, surgical, pathological, molecular, and imaging data were analyzed. Tumor response was evaluated on MRI. RESULTS:During the study period, 60 patients with medulloblastoma were treated at the medical center; 12 male patients (mean age 6.5 years, range 1.1-16.1 years) with metastatic disease who were treated with the upfront biopsy-only approach met the inclusion criteria. The median follow-up duration was 3.2 years. At the time of analysis, 9 patients (75%) were alive, with an estimated 5-year survival rate of 63%, and 3 patients had died (2 with very high-risk MYC-amplified tumors and 1 with a late supratentorial relapse). No cases of posterior fossa syndrome were observed. All surviving patients showed stable or resolving residual abnormalities on MRI without progressive disease. CONCLUSIONS:In pediatric patients with metastatic medulloblastoma, primary tumor resection might be avoidable. A biopsy-based approach followed by timely multimodal therapy can preserve survival outcomes while minimizing surgical risks, as long-term prognosis is likely related to the disease subtype and prompt oncological treatment. The proposed strategy warrants further investigation and might have broader implications for medulloblastoma treatment paradigms.

The role of FDG-PET in the restaging rectal cancer following neoadjuvant therapy (NAT) is not clear. We compared the accuracy of FDG-PET and MRI in the assessment of rectal cancer response to NAT. Data of patients treated between January 2015 and September 2022 were captured from a rectal tumor registry. Restaging FDG-PET and MRI were evaluated for the presence of viable tumor. Imaging was compared to the reference standard of pathological results for patients that underwent surgery, and sustained clinical complete response for patients that entered watch and wait. Sensitivity was defined as correctly identifying patients with a complete response. Eighty-two patients met the inclusion criteria. Of these, 60 patients underwent restaging MRI and 54 underwent restaging FDG-PET. Thirty-two were evaluated by both modalities. Mean age and distance from anal verge were 59.9 ± 12.7 years and 5.9 ± 3.2 cm. Baseline staging was cT1-2, cT3 and cT4 for 7 (8.5%), 62 (75.6%) and 13 (15.9%) of the patients, respectively. Baseline nodal staging was cN0 and cN + for 32 (39%) and 50 (61%) of the patients, respectively. All patients were treated with radiation with the majority 73 (89%) receiving chemoradiotherapy. There were 17 patients (21%) that had a pathological or sustained clinical complete response. All baseline characteristics were not meaningfully different between groups. MRI was more accurate than FDG-PET in all parameters including sensitivity, specificity, positive and negative predictive value and overall accuracy. MRI outperforms FDG-PET in the identification of complete response in rectal cancer patients after NAT.

Objectives To investigate the presentation, treatment, and outcomes of head and neck squamous cell carcinoma (HNSCC) in patients with Fanconi anemia (FA), a rare genetic disorder characterized by increased cancer risk and treatment complications. Methods We conducted a retrospective cohort study of 11 FA patients diagnosed with HNSCC across five XXX medical centers from 2014 to 2023. Data on patient demographics, tumor characteristics, treatment modalities, complications, recurrences, and survival outcomes were analyzed using descriptive and survival statistics. Results FA patients developed HNSCC at a median age of 31.5 years, primarily in the oral cavity. Surgical treatment was the primary treatment modality; however adjunct radiotherapy resulted in severe complications, such as high-grade mucositis in 75% of cases. Median overall survival was 28.7 months, with 36.4% of patients succumbing within 12 months of diagnosis. Recurrences were noted in three patients, split equally between local and distant sites, and 36% developed secondary malignancies up to 17 years post-initial diagnosis. Conclusions HNSCC in FA patients presents distinct challenges, including a younger onset age, high rates of severe treatment complications, and poor survival outcomes. Tailoring treatment strategies to minimize radiotherapy exposure and implementing rigorous, long-term surveillance for second malignancies are essential for managing these high-risk patients. Level of Evidence: Level IV.

Introduction - Patients aged over 70 years with relapsed or refractory acute myeloid leukemia (AML) have an extremely poor prognosis, with median overall survival of only 2 months using standard care approaches. Given the limited efficacy of salvage chemotherapy in this population and the low likelihood of long-term survival, we adopted a modified reduced-intensity conditioning (RIC) regimen—FITCy (fludarabine, cytarabine ± idarubicin, and cyclophosphamide with 4 Gy total body irradiation)—in elderly patients with available donors, aiming to proceed directly to allogeneic hematopoietic cell transplantation (HCT) despite active disease. Methods – All patients who were diagnosed with AML and were above the age of 70 years, were identified by the transplantation coordinator nurse and underwent donor evaluation within 2 days from diagnosis. Patients treated with 7+3 or venetoclax-azacitidine underwent bone marrow assessment on day 14 or day 21, respectively. In cases where leukemic blasts were detected, donor search was promptly prioritized. These patients went on to have a day 28 bone marrow examination to confirm refractory disease. All consecutive patients, diagnosed with either primary refractory or relapse AML, underwent HCT with the FITCy regimen in the Tel Aviv Sourasky Medical Center. The protocol was amended on January 2018 to include ATG for all patients after interim analysis showed a high rate of GVHD. Venetoclax was added for the first 12 days of preparative regimen since January 2020 to increase efficacy. Results– Between January 2014 and December 2024, 51 patients were identified with primary (n=35)/relapse (n=16) refractory disease and were treated with the FITCy regimen. Twenty-three (45%) patients were treated with venetoclax-based induction therapy. Median age was 72 (range, 70-78) years. Median Karnovski score and HCTCI were 80% (range, 50%-90%) and 3 (range, 0-8), respectively. The majority of patients (n=36, 71%) received an allograft from a matched unrelated donor. Median follow-up was 34 (range, 10-91) months. Median days to engraftment of neutrophils (>500/dL) and of platelets (>20000/dL) were 11 (range, 9-21), and 15 (9-37) days, respectively. No patient had primary/secondary graft rejection. Severe mucositis was observed in only 2 patients (4%) and was mostly observed in the lower gut. Three (6%) patients developed sinusoidal obstruction syndrome and 15 (29%) patients developed microbiology documented infections during the neutropenic period, leading to death in 3 (6%). Among the 48 evaluable patients on day 30, 46 (90%) patients had complete remission state, and median whole marrow donor chimerism of 98% (range, 84%-100%). Cumulative incidences of grade 2-4 and 3-4 acute GVHD by day 200 were 57%(95%CI 41%-72%) and 9%(95%CI 3%-22%), respectively. Cumulative incidences of overall and moderate-severe chronic GVHD at 1 year after HCT were 35%(95%CI 2%-52%) and 26%(95%CI 15%-43%), respectively. Cumulative incidences of relapse at 1 and 3 years post HCT were 22%(95%CI 12%-35%) and 27%(95%CI 17%-41%), respectively. There was 1 case of relapse beyond 5 years from HCT. Non-relapse mortality rates, at 30 days, 100 days and 1 year post HCT were 10% (95%CI 3%-21%), 25% (95%CI 15%-40%), and 35% (95%CI 23%-52%), respectively. Incidences of GVHD-relapse-free survival at 1 and 3 years were 39% (95%CI 21%-48%) and 29% (95%CI 15%-42%), respectively. In the Cox regression model, venetoclax-based induction therapy (HR=.35, p=.03), primary refractory disease (as opposed to relapse disease, HR=.27, p<.001), and ATG (HR=.19, p=.005) were associated with improved GRFS, while addition of venetoclax to the preparative regimen, sex, age, and HCTCI had no effect. Cumulative incidences at 1- and 3-years overall survival were 53%(95%CI 37%-65%) and 42%(95%CI 13%-49%). In the Cox regression model, venetoclax-based induction therapy (HR=.26, p=.014), primary refractory disease (HR = 0.23, p<.001), ATG (HR=.17, p=.003), and lower HCTCI (HR=.67, p=.04) were associated with improved OS, while addition of venetoclax to the preparative regimen, age, and sex had no effect. Conclusions – Sequential therapy in elderly patients with active AML demonstrates a strong anti-leukemic effect. Improved GVHD prophylaxis and early referral (primary vs. relapse setting) were associated with better GRFS and OS. Age alone should not be a barrier to this strategy, though it must be weighed against emerging targeted therapies.

Background Lymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy. We hypothesized that chronic lymphopenia following radiotherapy might negatively influence the survival of patients, and pre-treatment lymphopenia may be predictive of poor outcomes. Methods This retrospective study involved 110 patients treated for rectal cancer between 2015 and 2019. The oncological outcomes are defined as alive without disease (AWOD), alive with disease (AWD), and death. These outcome probabilities tested against variables of lymphopenia before RT, during RT, and at several post-RT follow-up time points. Results At the end of the study, 69 patients were AWOD (63 %), 13 were AWD (12 %) and 28 had died (25 %). Treatment results were assessed with according level of lymphocytes measured one year following RT: 35 out of 39 patients (89.7 %) with normal values were AWOD. In 65 patients with sustained lymphopenia, 52 % were AWOD, 18.5 % AWD and 29 % died. A similar difference was found at all time-points up to 2 years following RT (p < 0.004).The results of our study shows that pre-existing lymphopenia (prior to RT) is associated with a 3 times greater chance of death compared to patients with normal lymphocyte levels prior to RT. The PFS significantly affected by lymphopenia at all time-points after RT. An NLR of more than 4 was associated with a 3-time higher risk of recurrence than lower NLR scores (p = 0.0054). Conclusion Our results support the relevance of lymphopenia and NLR in the prognosis of rectal cancer. We believe this is the first study showing a negative correlation between sustained lymphopenia and OS following RT.

Background: Cutaneous squamous cell carcinoma (cSCC) is characterized by a high tumor mutational burden due to solar damage and a favorable response to anti-PD-1 immunotherapy. Yet, we encounter tumors arising in areas with minimal sun exposure, such as cSCC that develops in chronically inflamed skin, also known as Marjolin's Ulcer (MU). The response of MU-SCC to immunotherapy remains unknown. Methods: We performed a retrospective analysis of patients diagnosed with cSCC and treated with cemiplimab or pembrolizumab in a single tertiary medical center. Patients lost to follow up were excluded. Results: Of the 84 eligible patients, 9 (11%) had MU-SCC. Of these, 2 (22%) reached partial response (PR), and none reached complete response (CR). In contrast, of the 75 patients with solar damage-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P < .001). Interestingly, 3 patients with MU-SCC received a second-line chemo-immunotherapy and experienced a partial response that continued for 5 to 21 months. Patients with MU-SCC had a significantly shorter median time to progression (TTP) (1.6 vs 51.6 months, P < .001) and progression-free survival (PFS) (1.6 vs 15.4 months, P < .001). Overall survival (OS) was not significantly shorter (17.4 vs 36.7 months, P = .096). Multivariate analysis confirmed that MU-SCC is an independent risk factor for shorter TTP (HR 5.5, 95% CI 2.2-14.0, P < .001) and PFS (HR 3.5, 95% CI 1.5-8.1, P = .003). Conclusions: This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

e21559 Background: Cutaneous squamous cell carcinoma (cSCC) represents a favorable tumor microenvironment with high tumor mutational burden, and infiltration of immune cells that are highly responsive to immunotherapies. Yet, we encounter tumors arising on non-exposed skin, such as those developing from chronic ulcers in which the response to anti-PD1 is unknown. Methods: The authors reviewed the medical records of consecutive cSCC patients receiving Cemiplimab or Pembrolizumab at a single tertiary center. Results: Of the 84 eligible patients, 9 (11%) had ulcer-related cSCC. six out of the nine (67%) were located on the lower extremities. Only two out of these nine patients (22%) reached partial response (PR) and none reached complete response (CR). In contrast, of the 75 patients with non-ulcer-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P < 0.001). Interestingly, two of the seven non-responders in the ulcer-related subtype received second-line chemo-immunotherapy and experienced a partial response that continued for 21 and 8 months. Patients with ulcer-related SCC had a significantly shorter median progression-free survival (PFS) (2.1 months vs. non-reached, p < 0.001). Overall survival (OS) was also shorter, but didn't reach significance (17 vs. 30 months, p = 0.02). Multivariate analysis confirmed ulcer-related SCC as an independent risk factor for shorter PFS (hazard ratio [HR], 7.56; 95% confidence interval [CI], 1.26-40.74, p = 0.027). Conclusions: This study suggests immunotherapy is less beneficial in ulcer-related SCC. More work is needed to verify our findings and explore other treatment options including chemoimmunotherapy.

Background Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated. Methods A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared. Results Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p = 0.015). Conclusion Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.

Background and purpose: Myeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children. Material and methods: The European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established. Results: Myeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3-4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III-IV evidence. Preferential TBI dose in children is 12-14.4 Gy in 1.6-2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to <10 Gy, and for the lenses to <12 Gy, for dose rates >6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies.

Introduction - primary refractory AML is associated with a dismal prognosis. Only 30% of patients will respond to salvage chemotherapy and continue to allogeneic hematopoietic cell transplantation (HCT) with a 10-20% long- term overall survival. Following from the FLAMSA protocol, we implemented a modified RIC regimen - FITCy (fludarabine, cytarabine +/- idarubicin and 4 Gy TBI) in all primary refractory patients with a donor available for transplant.

Introduction: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. Materials and Methods: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015–2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. Results: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 <55%, while its role in limited disease was nonsignificant. Discussion: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

Purpose Over recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose. Methods In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177 Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method. Results Differences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater. Conclusion This study indicates that for 177 Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.

Background and purpose: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers. Methods: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously. Results: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated <= 10 pediatric patients annually (range: 1-2 to >25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques. Conclusion: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI. (C) 2020 The Author(s). Published by Elsevier B.V.

Introduction: Rectal cancer is a common and lethal disease, with approximately 44,180 new cases of diagnosed annually in the United States and a five-year survival of 67% [1, 2]. The interval from diagnosis to chemoradiation treatment, or waiting time (WT), is considered to be an important quality indicator for cancer care and has been demonstrated to be associated with oncologic outcomes in various cancers [3, 4]. The current recommendation for pre-treatment staging evaluation includes rigid proctoscopy, PET CT, transrectal ultrasound (TRUS) and often rectal MRI. These diagnostic procedures may significantly postpone the start of treatment. We aim to examine the effect of WT on overall survival (OS) and disease free survival (DFS) of rectal cancer patients. Methods: Retrospective analysis was performed in a detailed database of patients with resectable primary rectal cancer who underwent chemoradiation between January 2000 and January 2019. Univariate and multivariate cox proportional hazard regressions were conducted in order to evaluate the effect of WT on oncological outcomes. Results: 387 patients were enrolled in our database; of them 297 patients were eligible by the inclusion criteria. Median WT was 6.3 weeks (IQR 4.3-8.7). Multivariate analysis showed adjusted Hazard Ratio (HR) for OS increases by 1.07 for each additional week of therapeutic delay in all age groups (p=0.025). Furthermore, focusing on the majority of patients in the age group 45 - 70 years, adjusted HR for OS increases by 1.12 for each additional week of therapeutic delay (p=0.011). Adjusted HR for DFS increases by 1.06 for each additional week of therapeutic delay in all age groups (p=0.045) and an increment by 1.09 for each additional week of therapeutic delay in age group 45-70 years (p=0.02). Conclusion: Prolonged WT leads to significant poorer overall survival in patients with primary rectal cancer who underwent chemoradiation and curative surgical treatment. This marks the importance of efficient diagnostic evaluation and clinical multidisciplinary decision making in a timeframe of 6 weeks in order to not jeopardize oncological outcomes.

Abstract INTRODUCTION Metastatic medulloblastoma is a challenging disease The current clinical approach advocates removal of the primary tumor in the posterior fossa despite evidence of metastatic disease and administer oncologic treatment within several weeks: Infants of 3–4 years are treated by tandem high dose chemotherapy with stem cell support (ACNS0334 protocol), while older children are given radiotherapy and tandem high dose chemotherapy with stem cell support (SJMB03 protocol). We postulate that a resection of the primary tumor is not obligatory, and a biopsy may suffice in order to enable prompt oncological treatment without affecting the long-term survival. PATIENTS AND METHODS Between 2010-2019 7 patients with metastatic medulloblastoma (median age 4.5, age 1–10) were treated with biopsy only, five spinal and two from the primary tumor. Six children had a concurrent VP shunt. Four presented with cord compression, and two with neurological deterioration. Four needed emergency radiotherapy. Two infants received protocol ACNS0334, five patients received protocol SJMB03. RESULTS Six patients (85%) survived; .3 patients are long term survivors (> 5 years), 2 patients are in remission for 2–3 years, one patient is on active therapy. Only 1 patient died after a late (4 years) metastatic relapse not in the posterior fossa. CONCLUSIONS Metastatic medulloblastoma can be cured without excision of the primary tumor and without mutilating surgery. Long term prognosis is probably more attributable to disease subtype and prompt oncologic treatment. This approach merits further studies and may have implications on treatment of non-metastatic tumors.

e17582 Background: Salivary gland cancers (SGCs) are rare tumors. The approach to recurrent or metastatic patients is histology dependent, as the clinical course is highly variable. Response rates to chemotherapy are modest and no second-line therapies have proven to be effective. The rarity and heterogeneity of SGCs make conducting clinical trials challenging. Recent reports of Next Generation Sequencing (NGS) in SGCs have identified unique genetic attributes of certain histological classes. However, despite the elaborate work done with genetic characterization, there is very little evidence on whether these findings translate to tumor control. In this study, we aimed to explore the treatment outcomes of patients with advanced SGCs who underwent a commercially available NGS. Methods: A retrospective analysis of all patients with histologically confirmed SGC treated in three major Israeli cancer centers who underwent NGS. Results: Twenty-seven patients were included. Eighteen patients were male (66.6%). The median age was 59 (range 38-81). Histologic type was adenoid cystic carcinoma in 11 (40.7%) patients, 8 (29.6%) mucoepidermoid carcinomas, 5 (18.5%) adenocarcinomas, 2 (7.4%) salivary duct carcinomas and 1 (3.7%) acinic cell carcinoma. Twenty-five (92.6%) had recurrent disease after initial curative treatment and 2 were initially diagnosed with metastatic disease. Median time to recurrence was 24.3 months. The median number of systemic treatment lines was 1 (range 0-5). Thirteen patients (48%) had targetable findings in NGS, including: 5 ERBB2 amplifications, 3 PIK3CA mutation, 1 TRIM33-RET fusion, 1 FGFR3-TACC3 fusion, 1 MSI-high and 2 high mutational burden. Nine patients were treated accordingly; 5 in the second-line and 4 as first-line treatment. Median progression-free survival for targeted treatment was 8.4 months. Of 4 patients who achieved durable responses to anti-RET/HER2 agents and immunotherapy of 8.4 – 31.1 months, two are ongoing. The median overall survival for all patients was 101.75 months, was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (p = 0.26). Conclusions: In the absence of a well-established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGCs.