Disease Control Outcomes Research Articles

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer.

PurposeStereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.Methods and MaterialsThis study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally important difference (MID) assessing patient-reported quality of life was defined as greater than a one-half standard deviation increase in American Urological Association (AUA) symptom score after SAbR.ResultsTwo-hundred and forty-nine (249) low-, intermediate-, and high-risk PCa patients with median follow-up of 14.9 months for clinical toxicity were included. Acute urinary grade II toxicity occurred in 20.4% of patients. Acute grade II GI toxicity occurred in 7.3% of patients. For follow-up > 2 years (n = 69), late GU and GI grade ≥III toxicity occurred in 5.8% and 1.5% of patients, respectively. MID was evident in 31.8%, 23.4%, 35.8%, 37.0%, 33.3%, and 26.7% of patients at 3, 6, 12, 24, 36, and 48 months, respectively. The median follow-up for biochemical recurrence was 22.6 months with biochemical failure-free survival of 100% at 1 year (n = 226) and 98.7% for years 2 (n = 113) and 3 (n = 54).ConclusionsSAbR for PCa at 45 Gy in 5 fractions shows an encouraging safety profile. Prospective studies with longer follow-up are warranted to establish this dose regimen as standard of care for PCa.

Preliminary Results of Uveal Melanoma Treated With Iodine-125 Plaques: Analysis of Disease Control and Visual Outcomes With 63 Gy to the Target Volume

PurposeOur purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach. Methods and MaterialsThis was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis. ResultsSixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse. ConclusionsIn patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes.

Neoadjuvant Pelvic Radiotherapy in the Management of Rectal Cancer with Synchronous Liver Metastases: Is it Worth it?

Introduction: The use of neoadjuvant pelvic radiotherapy was a major advance in oncologic care for locally-advanced rectal cancer (RC) in the 20th century. The extrapolation of the care of locally-advanced RC to the management of RC with treatable liver metastases is controversial. The aim of this systematic review is to examine the available data on the role of pelvic radiotherapy and chemoradiation in the setting of treatable metastatic liver disease. Methods: A systematic review of MEDLINE was performed to report the landmark randomized controlled trials between 1993-2021. Results: Attaining liver clearance and total mesorectal excision with negative margin remains the mainstay of cure. There is uncertainty regarding the sequencing of treatment. The literature lacks randomized clinical trials comparing the rectal first, liver first, interval strategy and simultaneous surgical approaches. A multidisciplinary discussion regarding the utility of radiotherapy is emphasized to achieve the goals of treatment. Short-course radiotherapy has proved comparable disease-control outcomes to long-course chemoradiation with a significantly improved cost-performance. The implementation of short-course radiotherapy in the interval strategy and simultaneous surgical approach is promising. Neoadjuvant pelvic radiotherapy can be omitted in patients with metastatic RC if adequate margin clearance is achievable. Conclusion: The use of pelvic radiotherapy in metastatic RC is popular, but can be omitted when R0 resection can be achieved. Treatment should be tailored to the local extent of RC and priority of liver metastasis management. The optimal treatment strategy in patients with synchronous rectal liver metastases needs to be studied in randomized trials.

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases

Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively. Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach. ClinicalTrials.gov Identifier: NCT03074656.

Volumetric de-escalation and improved acute toxicity with proton craniospinal irradiation using a vertebral body-sparing technique.

In growing children, craniospinal irradiation (CSI) has historically treated the entire vertebral body (VB) to avoid potential long-term spinal abnormalities. Vertebral body-sparing proton craniospinal irradiation (VBSpCSI) is a technique that spares the majority of the VB from significant irradiation, and long-term safety outcomes have been reported previously. This retrospective study reviews the acute toxicity profile of children treated with VBSpCSI in a cohort comparison with photon-based craniospinal radiotherapy (3DCRT). Thirty-eight pediatric CSI patients treated between 2008 and 2018 were retrospectively evaluated for treatment-related toxicity. Acute toxicity outcomes and acute hematologic profiles were compared according to treatment modality, either VBSpCSI or 3DCRT. Statistical analysis was performed using Fisher's exact test for toxicity. Twenty-five patients received VBSpCSI and 13 patients received photon CSI. Mean patient age at treatment was 7.5years (range 2-16). The cohorts were well matched with respect to gender, age, and CSI dose. Patients receiving VBSpCSI had lower rates of grade 2+ gastrointestinal (GI) toxicity (24% vs. 76.5%, p=.005), grade 2+ nausea (24% vs. 61.5%, p=.035), and any-grade esophagitis (0% vs. 38%, p=.0026). Patients treated with VBSpCSI had lower red blood cell transfusion rates (21.7% vs. 60%, p=.049) and grade 4+ lymphopenia (33.3% vs. 77.8%, p=.046). VBSpCSI in children is a volumetric de-escalation from traditional volumes, which irradiate the entire VB to full or intermediate doses. In our study, VBSpCSI was associated with lower rates of acute GI and hematologic toxicities. Long-term growth outcomes and disease control outcomes are needed for this technique.

Radiotherapy alone for pediatric patients with craniopharyngioma.

Radiotherapy alone, without tumor-directed surgery, may be appropriate for selected patients with craniopharyngioma reducing the risks associated with neurosurgery. Understanding outcomes for patients with craniopharyngioma treated with radiotherapy alone will further refine patient selection and treatment options. Since 2002, 13 children, adolescents and young adults, with craniopharyngioma were treated with radiotherapy alone and followed for disease control and functional outcomes at a single institution. The median age at treatment was 13years (range, 3-21years). All patients received 54Gy/54Gy(RBE) in 30 fractions. Five patients were treated with intensity-modulated photon therapy, four with passively scattered proton therapy, and four with intensity-modulated proton therapy. With a median follow-up of 5years (range 3months-14years), all patients were alive. One experienced tumor progression 8.5years after treatment. No significant changes in vision, hearing or neurologic function attributed to radiotherapy. Hormone deficiencies and body mass index were within the expected range at baseline and 5years after treatment. There was no evidence of cognitive decline based on assessment of IQ, memory and attention. Unexpected complications included single cases of out-of-field malignancy, white matter changes, large vessel narrowing, and pontine capillary telangiectasia. Six patients had sphenoid bone abnormalities on follow-up imaging attributed to radiotherapy. Radiotherapy alone is an important treatment option to consider when radical resection is contraindicated, or surgical intervention is not required to alleviate symptoms. Disease control and functional outcomes are excellent after radiation therapy alone in appropriately selected patients.

RADT-25. PROTON THERAPY FOR YOUNG ADULT MEDULLOBLASTOMA: ACUTE TOXICITY AND DISEASE CONTROL OUTCOMES

Abstract BACKGROUND Report disease control, survival outcomes, and acute radiotherapy related toxicity among young adult medulloblastoma patients who received proton craniospinal irradiation (CSI) as part of multimodality therapy. We reports the completion rates of planned adjuvant chemotherapy. METHODS All adult medulloblastoma patients (≥ 22 years old) who received postoperative proton CSI +/- chemotherapy at our institution between 2008 and 2020 were included. Patient, disease, and treatment details along with prospectively obtained patient-reported acute CSI toxicities were collected (CTCAE v3 or v4). Acute hematologic data were analyzed. RESULTS Twenty young adult medulloblastoma patients were included. The median age at diagnosis was 27 years (range, 22–30). 45% had high-risk disease. 75% received chemotherapy, most of whom (65%) received post-CSI chemotherapy. Eight patients (40%) received concurrent vincristine with CSI. The median CSI dose was 36 GyE (range, 23.4-36) with a median tumor bed boost of 54 GyE (54-55.8). The median duration of radiotherapy was 44 days (range, 40-49). There were no acute ≥ grade 3 gastrointestinal or hematologic toxicities attributable to CSI (during or within 4 weeks after completion of RT). Grade 2 nausea and vomiting affected 25% and 5% of patients, respectively. Acute grade 2 hematologic toxicity affected 36% of patients. Among patients planned to receive adjuvant chemotherapy (n=13), 100% completed at least 4 cycles and 85% completed all planned chemo cycles. With a median follow-up of 3.1 years, 4-year actuarial local control, DFS, and OS were 90% (95% CI 53-99), 90% (95% CI 53-99), and 95% (95% CI 72-99), respectively. Two patients had disease recurrence, both with local failures in the high dose boost volume in the tumor bed. CONCLUSIONS Proton radiotherapy for CSI in young adult medulloblastoma patients is well tolerated and shows promising disease control and survival outcomes. These data support the standard use of proton CSI for adult medulloblastoma.

Radiomics for Predicting Lung Cancer Outcomes Following Radiotherapy: A Systematic Review

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms ‘radiomics’ and ‘lung cancer’ according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15–645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21–295). The median number of imaging features extracted was 184 (10–6538). The median Radiomics Quality Score was 11% (0–47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Final Report of NRG Oncology RTOG 0022: A Phase I/II Study of Conformal and Intensity Modulated Radiation for Oropharyngeal Cancer

Final Report of NRG Oncology RTOG 0022: A Phase I/II Study of Conformal and Intensity Modulated Radiation for Oropharyngeal Cancer

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy.

PurposeLong-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment.MethodsOne hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS.ResultsThe median length of follow-up was 8.3 years (range, 1.2–10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05).ConclusionDisease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies.

Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma

Immune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7–14.3). Median overall survival was 13.0 months (95% CI NE–NE), 9.0 months(95% CI 6.3–11.7)and 3.0 months (95% CI 1.9–4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI 2.9–7.1, p < 0.001), 4.0 months (95% CI 2.8–5.2) and 2.0 months (95% CI 1.7–2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1–91.6, p < 0.001; 54.3%, 95% CI 36.6–71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI NE–NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI 0.9–3.1) and sintilimab group (2.0 months, 95% CI 0.8–3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.

Management of parapharyngeal space tumors with transparotid–transcervical approach: analysis of prognostic factors related with disease-control and functional outcomes

Different therapeutic strategies have been developed to improve surgical and functional outcome of parapharyngeal space (PPS) neoplasms. The transparotid-transcervical approach (TTa) is a valid surgical option to manage most PPS tumors. Its short- and long-term disease control and cranial nerve (c.n.) function outcomes have not been discussed extensively. All patients who underwent TTa over a 10-year period at a tertiary academic center were retrospectively reviewed. Data about preoperative imaging, clinical presentation, tumor's size, location and histology, and postoperative oncological and functional results were registered and analyzed. Sixty patients matched the inclusion criteria. Most of the lesions were benign (71.7%), involved the prestyloid PPS (63.3%) and measured more than 30mm (75%). Fifty-two (86.7%) lesions were resected en-bloc. Clear margins were achieved in 91.7% of the cases, with positive margins solely associated with malignancy (p = 0.008). Post-operative c.n. function was satisfactory, with X c.n. function significantly associated with the retrostyloid location (p = .00) and neurogenic tumors (p = 0.02). Local disease-control was achieved in 96% of the cases after a median follow-up of 46 (± 19.7-82.0 IQR) months. The TTa was safe and effective, achieving a satisfactory local control rate. Nevertheless, malignancies maintain a higher rate of positive margin due to their infiltrative nature and the complex anatomy of the PPS. In such cases, multiportal approaches might be more effective. However, post-operative c.n. function remained satisfactory, irrespective of lesions' size and histopathologic behavior. A higher X c.n. deficit rate was observed in retrostyloid and neurogenic lesions.

Functional gland-preserving surgery via periauricular incision for pleomorphic adenoma of the parotid gland

IntroductionGland-preserving surgery is often used for benign tumours in the parotid gland. Partial superficial parotidectomy via a periauricular incision may bring satisfactory cosmetic outcomes but the disease control outcome remains unrevealed. This study evaluated functional and disease control outcomes after gland-preserving surgery via periauricular incision for pleomorphic adenoma of the parotid gland. MethodsThis longitudinal study included 248 consecutive patients with parotid pleomorphic adenoma who underwent the preservation of most normal parotid tissues and the facial nerve combined with the en-bloc resection of tumours via periauricular incision. Postoperative complications, subjective satisfaction, salivary function, and tumour recurrence were assessed in each patient. The secretory function of the salivary gland was measured using salivary scintigraphy at 6 months after surgery, and ultrasonography was regularly followed. ResultsMedian tumour size was 2.5 cm (range, 0.8–5.2 cm) and median operation time was 55 min (range, 39–88 min). All tumours were safely removed by gland-preserving surgery via periauricular incision without extension to Blair or hairline incision and tumour spillage. Temporary and permanent paralysis of the facial nerve was 14 (5.6%) and none of the study patients, respectively. Postoperative complications were minor and Frey's syndrome was found in 6 (2.4%) patients. The Secretary function of the affected gland was equal to that of the unaffected gland. No patients had a recurrence for a median follow-up of 78 months (range, 24–126 months). ConclusionsFunctional gland-preserving surgery via periauricular incision can treat pleomorphic adenoma in the parotid gland with satisfactory functional, cosmetic, and disease control outcomes.

Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma.

Background: Plasmacytoid dendritic cells (pDCs) play prominent roles in mediating innate and adaptive immune responses. However, it is unclear how pDCs contribute to the immunosuppressive tumor microenvironment described in multiple myeloma (MM). Methods: Newly diagnosed myeloma patients (MM, n = 37) were analyzed to determine the pDC counts in comparison to peripheral blood (PB, n = 53) and bone marrow (BM, n = 10) samples of age-matched healthy donors (HD) using flow cytometry. Second, proliferation of myeloma tumor cells in the presence of freshly isolated pDCs was examined. Third, production of IFNα by pDCs co-cultured with MM cells was determined by intracellular staining. Results: We found a highly significant reduction of circulating pDCs (p < 0.0001) and in bone marrow (p < 0.0001) of MM patients compared to HD. We also observed a significant decrease of pDCs (p = 0.004) in BM in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 12). Importantly, we determined that pDCs promote proliferation specifically of MM cells and not the stromal cells and that pDCs secrete IFNα upon co-culture with MM tumor cells. Conclusions: Our results show altered pDC frequencies in the BM microenvironment in MGUS and MM patients at diagnosis. We showed the tumor-promoting function of pDCs that may mediate immune deficiencies affecting long-term disease control and treatment outcome.

Treatment Outcomes of Head and Neck Cancer Patients in the Elderly Receiving Different Chemoradiation Combinations: A Single-Center Experience

Objectives: This study aimed to assess the effect of definitive or adjuvant concurrent chemoradiation (CRT) among elderly patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Materials and Methods: We retrospectively analyzed 150 elderly LA HNSCC patients (age ≥70) at a single institution. Demographics, disease control outcomes, and toxicities with different chemotherapy regimens were reviewed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) estimates. Results: Median age at diagnosis was 74 years (range 70–88). Of the cohort, 98 (65.3%) patients received definitive and 52 (34.7%) received adjuvant CRT; 44 (29.3%) patients received weekly carboplatin and paclitaxel, 43 (28.7%) weekly cetuximab, 33 (22%) weekly carboplatin, and 30 (20%) weekly cisplatin. The OS at 2 years was 70% (95% confidence interval [CI]: 63–79%), and PFS at 2 years was 61% (95% CI: 53–70%). There was no significant difference in OS or PFS between definitive and adjuvant CRT (p = 0.867 and p = 0.475, respectively). Type of chemotherapy regimen (single-agent carboplatin vs. others) (95% CI: 1.1–3.9; p = 0.009) was a key prognostic factor in predicting OS in multivariable analysis. Concurrent use of cetuximab was associated with increased risk of PEG tube dependence at 6 months (p < 0.001). Conclusions: Management of LA HNSCC in the elderly is a challenging scenario. Our study shows that CRT is a feasible treatment modality for elderly patients with LA HNSCC. We recommend CRT with weekly cisplatin or weekly carboplatin and paclitaxel. A chemotherapy regimen should be carefully selected in this difficult to treat population.

Perspective: Correlation Between Intracranial Pressure and Venous Sinus Pressures in Idiopathic Intracranial Hypertension

Resection of intramedullary spinal ependymomas carries great risk of postoperative neurological deficits. The objective of this study was to describe our experience using co-neurosurgeon teams to address intramedullary ependymomas to determine if the use of 2 experienced attending neurosurgeons with expertise in both neurosurgical oncology and spine pathology can improve outcomes for intramedullary ependymoma resections.We retrospectively compared surgical and disease control outcomes in intramedullary ependymoma cases performed by co-neurosurgeon (one neurosurgical oncologist and one neurosurgeon trained in spinal surgery) and single-neurosurgeon teams over a 13-year period at a single institution.Co-neurosurgeons performed resections in 34 (47.9%) patients, and a single neurosurgeon performed resections in 37 (52.1%) patients. There were no significant differences in the frequency of gross total resection in the co-neurosurgeon versus single-neurosurgeon group (85.7% vs. 78.4%, P = 0.45). Posterior spinal fusion was more common in the co-neurosurgeon group (35.3%) compared with the single-neurosurgeon group (8.1%) (P = 0.01). Two (5.9%) patients in the co-neurosurgeon group and 5 (13.5%) patients in the single-neurosurgeon group had complications requiring surgical revision (P = 0.28). Recurrence rates were similar in both groups (5.9% vs. 10.8%, P = 0.50). At last follow-up, 76% of patients who presented with mild or no deficits remained functionally independent.Resection of intramedullary ependymomas by co-neurosurgeon teams resulted in similar rates of gross total resection, postoperative complications, and recurrence compared with surgeries performed by a single neurosurgeon. Functional neurological outcomes were not impacted by co-neurosurgeons performing ependymoma resections.

Chemoradiotherapy with high-dose cisplatin compared with weekly cisplatin for locally advanced head and neck squamous cell carcinoma.

Concurrent chemoradiotherapy (CRT) using high-dose cisplatin (HDC) is standard for patients with locally advanced head and neck squamous cell carcinoma (HNSCC); weekly cisplatin (WC) is an alternative. We aim to compare retrospectively the survival and disease control outcomes between these regimens in our institutional experience. Patients with stage III-IV HNSCC treated with definitive or postoperative CRT between 2012 and 2018 were identified. Patients were stratified by intent-to-treat CRT. Overall survival (OS) and disease-free survival (DFS) were generated and multivariable Cox models were performed. 193 patients were treated with concurrent HDC (n=69), WC at 40mg/m2 (WC40, n=88) or WC at <40mg/m2 (WC<40, n=36). Treatment intent was definitive in 74% and adjuvant in 26%. Baseline differences included age, performance status and HPV status. Cumulative cisplatin dose ≥200mg/m2 was achieved in 89% (HDC), 86% (WC40) and 25% (WC<40, P<0.0001). For HDC, WC40 and WC<40, 2-year OS rates were 87%, 77%, 60% and 2-year DFS rates were 75%, 68% and 52%, respectively. Multivariable analysis revealed gender, performance status, primary site, T/N stage and chemotherapy as predictive of OS. Primary site, T/N stage and chemotherapy regimen were associated with DFS. Compared with HDC, no differences in locoregional control (LRC) or distant metastasis were observed between groups. Concurrent HDC is associated with increased total cisplatin intensity, OS and DFS compared with weekly cisplatin regimens. LRC was not associated with chemotherapy regimen. HDC remains the standard of care; WC40 is a reasonable alternative that does not appear to sacrifice LRC.

Double Endoprosthesis in the Management of Refractory Metastatic Primary Bone Tumors in Children and Young Adults.

Background Although not all children can be cured yet, much more emphasis is placed on the quality of life during and after cancer treatment. In the case of recurrence, mutilating treatment is still the prevalent option. In our study, we explored the role of limb salvage surgery for young patients with metastatic malignant bone tumors after endoprosthesis reconstruction during the first line of treatment and evaluated the impact of the local control modality in disease control and functional outcomes. Materials and Methods Eleven patients with bone tumor treated between 2007 and 2018 were included in this study. Both during primary treatment and during recurrence, limb salvage surgery was performed using a modular or expandable custom-made replacement system. Peri- and postoperative care for both surgeries were similar. All patients were given chemotherapy before and after both surgeries, according to the oncological guidelines. Results Seven patients (63.6%) are alive with a median follow-up of 6.5 years from diagnosis. None had local recurrence. Five-year estimates of event-free survival and overall survival were 36.27% and 79.55%, respectively. Median time between the first and second surgery was 2.7 years. Three patients presented with postoperative complications following both surgeries and required resurgical intervention. Three months following the second surgery, the Musculoskeletal Tumor Society Scale (MSTS) scores were 15–27 points (21 points on average—60%). Conclusions Limb salvage surgery is feasible and offers good chance of cure with a reasonable rate of complications and good function in patients with recurrent bone sarcoma after endoprosthesis reconstruction during the first line of treatment.

Inadequate Disease Control, Treatment Dissatisfaction, and Quality-of-Life Impairments Among US Patients Receiving Topical Therapy for Atopic Dermatitis.

IntroductionPatients with atopic dermatitis (AD) experience burdensome symptoms and impaired quality of life (QoL). The objective of this study was to investigate the effects of topical AD therapies on disease control, physician and patient treatment satisfaction, and QoL in a real-world setting.MethodsThis was a retrospective, point-in-time study of physician-completed medical records and patient surveys drawn from two Adelphi AD Disease Specific Programmes™ (1. adults ≥ 18 years old; 2. pediatrics ≤ 17 years old) in the USA. Eligible physicians completed patient record forms and provided disease control assessments. Physicians and matched patients were surveyed regarding their satisfaction with current treatment. Patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Children’s DLQI (CDLQI), Patient-Oriented Eczema Measure (POEM), and the Work Productivity and Activity Impairment (WPAI) questionnaire.ResultsA total of 394 adult (topicals only, n = 284; topical plus systemic, n = 110) and 144 adolescent (aged 12–17 years; topicals only, n = 114; topical plus systemic, n = 30) patients who had received their current treatment for at least 1 month were included. Overall, 24.5% of patients had physician-reported uncontrolled disease (adults, 22.8%; adolescents, 29.2%). Rates of physician- and patient-reported dissatisfaction with current treatment were 32.0% (adults, 28.2%; adolescents, 42.4%) and 24.8% (adults, 24.0%; adolescents, 26.8%), respectively, and were higher for patients with uncontrolled versus controlled disease. Poorer disease control and higher rates of treatment dissatisfaction were generally reported among patients receiving topical plus systemic therapy versus topicals alone. Patients with uncontrolled versus controlled disease reported more impairment in the DLQI, CDLQI, POEM, and WPAI (P < 0.05 for all), with generally greater impairments observed among patients on topical plus systemic therapy versus topicals alone.ConclusionPatients receiving topical AD therapies experienced uncontrolled disease and reported decreased overall functioning and lower QoL. An unmet need for topical AD treatments that improve disease control and patient outcomes exists.

Identification of Effective Combinations of Targeted Drugs for DNMT3A and NPM1 Mutated Acute Myeloid Leukemia

Abstract Introduction: As the molecular heterogeneity underlying cancer becomes better understood, the capacity to define actionable targeted therapeutic strategies for patients appears essential to improving outcomes. These challenges are exemplified in patients with acute myeloid leukemia (AML), where a broad spectrum of driver mutations, emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways frequently result in a lack of durable responses and rapid development of resistance to many single-agent targeted therapies. To identify biomarker-driven effective combination strategies for patients with AML, we built upon our previous ex vivo profiling of targeted drug combinations in primary patient specimens through integrated analysis of an expanded cohort of 133 AML patients. Methods: Freshly isolated primary mononuclear cells from patients were cultured in the presence of a panel of 48 drug combinations in fixed molar dose series encompassing different classes of targeted small-molecule inhibitors already approved by the FDA or in clinical development. For comparison, cells were also tested against graded concentrations of each single-agent, and sensitivity was assessed by MTS-based viability assay. IC50 and AUC values were derived using a probit regression model. Efficacy of each combination relative to its respective single-agents was calculated as a Combination Ratio (CR) value, defined as the combination IC50 or AUC divided by the lowest single-agent IC50 or AUC value, where a CR value Results: Analysis of our discovery cohort of 58 AML patients revealed several associations between molecular features and combination sensitivity. An intriguing finding was the significantly enhanced efficacy of combinations involving the bromodomain inhibitor, JQ1, in patients with mutations in NPM1 or DNMT3A. Specifically, the combination of JQ1 with the multi-kinase inhibitor sorafenib demonstrated superior efficacy compared to each inhibitor alone in patients with NPM1 mutations (median IC50 CR: 0.437; p=0.010). JQ1 paired with the CDK4/6 inhibitor, palbociclib, demonstrated superior efficacy compared with single-agents for patients with DNMT3A mutations (median IC50 CR: 0.119; p=0.017). These associations between the presence of NPM1 or DNTM3A mutations and increased JQ1-inclusive combination efficacy were also validated using our expanded AML cohort of 133 patients. For patients with NPM1 mutations, one-way ANOVA based comparison of AUC values for JQ1, sorafenib, and the combination showed JQ1 as the more effective of the two single agents, with the combination significantly reducing AUC beyond either drug alone (p Conclusions: Among the observed patterns of ex vivo drug combination efficacy associated with select, actionable diagnostic and genetic subsets in our study, our data suggest that AML patients harboring NPM1 or DNMT3A mutations demonstrate moderate sensitivity to the bromodomain inhibitor JQ1 and their viability is further inhibited by combinations of JQ1 with sorafenib or palbociclib, respectively. More broadly, these findings warrant clinical evaluation and highlight the utility of integrating drug sensitivity data with genomic information to identifying novel treatment strategies for improving disease control and patient outcomes. Disclosures Traer: ImmunoGen: Consultancy; Tolero: Consultancy; Notable Labs: Equity Ownership. Druker: Henry Stewart Talks: Patents & Royalties; MED-C: Membership on an entity's Board of Directors or advisory committees; MolecularMD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; McGraw Hill: Patents & Royalties; Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; The Leukemia & Lymphoma Society: Other: Joint Steering Committee of AML Master Protocol, Research Funding; Roche TCRC: Consultancy, Membership on an entity's Board of Directors or advisory committees; Third Coast Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Cylene: Consultancy, Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; Oregon Health & Science University: Patents & Royalties: #843 Mutated ABL Kinase Domains (licensed to various companies); #0996 Detection of Gleevec Resistant Mutations (licensed to various companies, including MolecularMD); #0606 Treatment of Gastrointestinal Stromal Tumors (exclusively licensed to Novartis); GRAIL: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Monojul: Consultancy; Millipore: Patents & Royalties: Royalties from Dana-Farber Cancer Institute, which has an exclusive commercial license with Millipore for monoclonal antiphosphotyrosine antibody 4G10, which I developed while employed at DFCI.; Baxalta US Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Tyner: Gilead: Research Funding; Incyte Corporation: Research Funding; Syros: Research Funding; Seattle Genetics: Research Funding; Leap Oncology: Consultancy; Aptose Biosciences: Research Funding; Array Biopharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Research Funding; Genentech: Research Funding; Takeda Pharmaceutical Company: Research Funding; Janssen Pharmaceutica: Research Funding; AstraZeneca: Research Funding.