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PURPOSE:Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR).METHODS:This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested.RESULTS:The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care.CONCLUSION:Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact.

Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

Bone pain is a common side effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study investigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain. This is a two-stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation (OBS) stage. Those who developed significant back or leg bone pain (SP) were enrolled into the treatment (TRT) stage and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score ≥5 and a 2-point increase after pegfilgrastim. The primary end point of TRT was reduction of worst back or leg bone pain with loratadine, defined as a 2-point decrease after treatment compared to OBS. Two hundred thirteen patients were included in the final analysis. Incidence of SP was 30.5 %. The SP subset had a worse overall Functional Assessment of Cancer Therapy-Bone Pain score (33.9 vs. 51.7, p

Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer. A man aged 57 years with a 35 pack-year smoking history presented with painless subacute paresthesia and weight fluctuation. A non-length-dependent small fibre neuropathy was confirmed by skin biopsy. Further testing revealed positive serum PCA-2 and CRMP-5 autoantibodies, which after positron emission tomography-CT led to histological confirmation of a small cell lung cancer. Initially, abnormal MRI and cerebrospinal fluid studies suggested central nervous system (CNS) involvement which was subclinical; however, 6 months later during antitumour therapy, the patient became symptomatic with choreoathetosis. After combined chemoradiation as well as immunosuppressive and symptomatic therapies, the clinical course stabilised, although residual neurological deficits remained at follow-up a year later. Coexistent PCA-2 and CRMP-5 autoantibodies may occur in the setting of small fibre peripheral neuropathy and choreoathetosis and predict cancer type. Two paraneoplastic syndromes can present successively over months; subclinical CNS involvement with evolving basal ganglia abnormalities can be a paraneoplastic manifestation. In the appropriate clinical setting, paraneoplastic testing should be considered in patients presenting with small fibre neuropathy.

9628 Background: Bone pain is a common side-effect of pegfilgrastim and can interfere with a patient’s quality of life and treatment adherence. Antihistamine therapy may have analgesic activity in ...

163 Background: Patients (pts) who fail to achieve pCR after neoadjuvant chemotherapy have a 20% risk of recurrence at two years. Data for effective postsurgical chemotherapy in this population is lacking. LDCM is an all-oral chemotherapy regimen with anti-angiogenic activity and acceptable toxicity in metastatic breast cancer. Aspirin is associated with a lower risk of breast cancer recurrence in retrospective studies and has anti-angiogenic activity. Here we combine LDCM and aspirin for high risk pts with poor response to neoadjuvant chemotherapy. Methods: Pts with stage II-III HER-2 negative breast cancer who had residual invasive cancer after neoadjuvant chemotherapy were eligible. Pts completed surgery and radiotherapy prior to enrolment and began study treatment within 180 days of surgery. Pts received four 28-day cycles of LDCM (cyclophosphamide 50 mg po daily, and methotrexate 2.5 mg po twice daily on days 1 and 2 each week ). Aspirin 325 mg daily was added on cycles 3 and 4. Pts were evaluated for the primary endpoint of toxicity and safety every 28 days. Secondary endpoint was 2 year relapse free survival. Results: 10 of 13 planned pts were evaluable for toxicity as of May 4, 2013. Pathologic stage ranged from T2N0 to T3N3. 70% of tumors were chemoresistant (stable or upstaged at time of surgery). 60% of pts had hormone receptor positive tumors and received concurrent hormonal therapy. Median age was 59 years (range 38-76). All pts completed 4 cycles of study treatment without dose reduction. There were no grade 3 or 4 related toxicities. Worst hematologic toxicity was grade 2 leukopenia. Worst nonhematologic toxicity was grade 2 fatigue; all other related toxicities were grade 1. 9 pts were evaluable for recurrence and one had recurred at a median followup of 16 months (range 10-26). Conclusions: This antiangiogenic regimen is well tolerated in patients at high risk for recurrence after neoadjuvant chemotherapy, resulting in one recurrence at 16 months median followup, and it may be a candidate for future trials in this setting. Subsequent analyses will include longer term followup and biomarkers for angiogenesis. Clinical trial information: NCT01612247.

e12000 Background: Patients (pts) who fail to achieve pCR after neoadjuvant chemotherapy have a 20% risk of recurrence at two years. Data for effective postsurgical chemotherapy in this population is lacking. LDCM is an all-oral chemotherapy regimen with anti-angiogenic activity and acceptable toxicity in metastatic breast cancer. Aspirin is associated with a lower risk of breast cancer recurrence in retrospective studies and has anti-angiogenic activity. Here we combine LDCM and aspirin for high risk pts with poor response to neoadjuvant chemotherapy. Methods: Pts with stage II-III HER-2 negative breast cancer who had residual invasive cancer after neoadjuvant chemotherapy were eligible. Pts completed surgery and radiotherapy prior to enrolment and began study treatment within 180 days of surgery. Pts received four 28-day cycles of LDCM (cyclophosphamide 50 mg po daily, and methotrexate 2.5 mg po twice daily on days 1 and 2 each week ). Aspirin 325 mg daily was added on cycles 3 and 4. Pts were evaluated for the primary endpoint of toxicity and safety every 28 days. Secondary endpoint was 2 year relapse free survival. Results: 10 of 13 planned pts were evaluable for toxicity as of Jan 24, 2013. Pathologic stage ranged from T2N0 to T3N3. 70% of tumors were chemoresistant (stable or upstaged at time of surgery). 60% of pts had hormone receptor positive tumors and received concurrent hormonal therapy. Median age was 59 years (range 38-76). All pts completed 4 cycles of study treatment without dose reduction. There were no grade 3 or 4 related toxicities. Worst hematologic toxicity was grade 2 leukopenia. Worst nonhematologic toxicity was grade 2 fatigue; all other related toxicities were grade 1. 9 pts were evaluable for recurrence and none had recurred at a median followup of 13 months (range 7-23). Conclusions: This antiangiogenic regimen is well tolerated in patients at high risk for recurrence after neoadjuvant chemotherapy, resulting in no recurrences at 13 months followup, and suggesting it may be a candidate for future trials in this setting. Subsequent analyses will include longer term followup and biomarkers for angiogenesis. Clinical trial information: NCT01612247.

Background: Mammographic density is an independent risk factor for breast cancer associated with a large relative and attributable risk for the disease. Given the prevalence of women with increased breast density, the attributable risk may be as high as 33%. The largest factor influencing density is heredity, but various lines of evidence suggest that modification of breast density is associated with a decrease in breast cancer risk. Studies have found vitamin D levels to be inversely related to breast density. Here we present a cross-sectional analysis of vitamin D and breast density in women enrolled in the Vermont Cancer Centers High Risk Breast Program. Longitudinal associations and correlations of vitamin D and breast density were evaluated. Methods: The High Risk Breast Program database, for women with strong family history, BRCA mutations, high risk pathology or prior chemoradiotherapy for Hodgkins Disease, was initiated in 2003 and contains over 500 women. A subset of 51 women ranging in age from 31-69 with a mean lifetime Gail risk of 21% is the subject of this analysis. Data collected included mammograms, a medical and dietary history, BMI, and serum Vitamin D levels. Breast density was interpreted (at baseline, 2 years and 4 years) from mammograms using a visual analogue scale and reliability was evaluated. Univariate and multivariate analyses were performed using SAS statistical software. Results: The intra-observer variability for density determination using a visual analogue scale was comparable to published studies (R=0.82). Baseline BMI showed an inverse univariate trend with percent of dense tissue at both time points (p=0.001). No correlation was found between any determinant and change in breast density measured at the 2 year time point. A subset of patients (n=37) was followed for 2 additional years. A model for change in percent dense tissue was obtained for this subset of patients using multivariate analysis that included baseline BMI and change in serum Vitamin D level (R2=0.23). The other factors with a univariate relationship were not found to contribute to the multivariate model. Conclusions: The HRBP database has become an invaluable resource, significantly reducing the financial resources necessary to complete this study and aiding the expansion of the study when needed. Information has been gained with high potential impact on prevention and early detection of breast cancer; first is the reproducibility of the visual analogue scale, a method of quantifying density which is readily available to clinicians and research staff with little training and minimal resources. Second, this study illuminates the importance of a longer follow up period for the detection of changes in mammographic breast density. Third, this study validates the association between serum vitamin D levels and percent breast density, and more importantly the inverse relationship between change in vitamin D levels and change in breast density. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 575. doi:1538-7445.AM2012-575

1556 Background: Breast density is an independent risk factor for breast cancer; associated with an OR ≥ 4 for very dense breast tissue. Given the prevalence of breast density, the attributable ris...