Utilization of cancer survivorship services during the COVID-19 pandemic in a tertiary referral center.

BACKGROUND: All Commission on Cancer-accredited comprehensive cancer centers offer survivorship programs (SPs) to women upon completion of treatment. These SPs can include clinical and non-clinical programming such as physical rehabilitation, emotional and psychosocial support, nutrition, and exercise programming. Concern about the availability and access to these programs during the COVID-19 pandemic has been described in recent literature. We sought to identify the impact of the COVID-19 pandemic on participation in these supportive services for breast cancer patients within a single institution. METHODS: The Ohio State University tertiary care center offers clinical and non-clinical breast cancer support services. Descriptive statistics were utilized to summarize referral and patient participation data from January 2019 through July 2021. Data from calendar year 2019 was used as a normative comparison for pre-COVID-19. In-person and telehealth use was tracked longitudinally. RESULTS: During the lockdown due to the COVID-19 pandemic (March through May 2020), provider referrals to SPs declined by 10%, while the overall total for the calendar year modestly increased from 1195 in 2019 to 1210 in 2020, representing a 1.3% increase. Psycho-oncology referrals increased from 280 to 318 (13.5%). The most significant change of participation rates in non-clinical SPs during the pandemic was utilization of exercise content, which increased by 220% from 2019 to 2020. The total proportion of breast cancer participants choosing an exercise program increased from 16.8% in 2019 to 42.2% in 2021, making it the most selected program area overall. Previously, nutrition was the most selected program area as it comprised 42.5% of overall utilization in 2019. CONCLUSION: The pandemic's potential to place barriers to participation in SPs is a legitimate concern. We found a modest decline in provider referrals to clinical services during the lockdown period, while patient-directed participation increased with more survivors engaging in exercise-based programs. Transitioning to virtual platforms served to maintain access for patients. IMPLICATIONS FOR CANCER SURVIVORS: As we grapple with the COVID-19 pandemic, patients with cancer deserve increased attention due to the expected stressors associated with the diagnosis. Those in the survivorship stage utilize services for psychosocial support, and the observed increase in utilization of SPs suggests an elevated need for connectivity. To meet this need, telehealth platforms have been expanded to allow for continued participation. It remains to be seen whether this will be sustained post-COVID-19 or whether reduced human contact will create new needs for programming.

Substance Use and Misuse: A Pilot Study to Improve Screening and Interventions at a Comprehensive Cancer Hospital.

Mounting evidence suggests patients diagnosed with cancer may be at increased risk for opioid misuse and diversion. Substance use disorders (SUDs), involving prescription medications and/or illegal substances, may significantly compromise the ability of healthcare professionals to deliver high-quality cancer care. A substance use screening pilot was conducted in ambulatory oncology clinics at a large cancer hospital in the midwestern United States. In this article, the authors present results from this quality improvement project. Future directions involve innovative methods to deliver addiction-specific knowledge to oncology healthcare providers and should focus on discussing screening results, as well as providing tailored recommendations using shared decision-making with patients and caregivers.

Evaluating Readability Scores of Treatment Summaries and Cancer Survivorship Care Plans.

PURPOSE: Treatment Summaries and Survivorship Care Plans (TS/SCPs) may be difficult for patients to comprehend because of readability, magnitude of information, and complex medical verbiage. METHODS: Readability scores were calculated for TS/SCP templates including ASCO, Oncolink, Journey Forward, and the authors' institution. The Simple Measure of Gobbledygook (SMOG) index, Flesch-Kincaid reading grade level, Coleman-Liau Index, and Gunning Fog index were used to assess readability. RESULTS: The Flesch-Kincaid reading ease scores for the blank ASCO templates ranged from 47.4 to 53.3, requiring a reading grade level of 10-12. Coleman-Liau and Gunning Fog scores showed that an 11th grade reading level is essential, and SMOG required a college education to comprehend the ASCO templates. For the colorectal case exemplar, Oncolink's template resulted in the lowest SMOG score (11.3; 11th grade), Flesch-Kincaid reading grade level (11; 11th grade), and Coleman-Liau score (12; 12th grade). Journey Forward's TS/SCP template scored the highest on the SMOG (21.2; college graduate), Flesch-Kincaid reading grade level (18.3; college graduate), and Gunning-Fog index (25.8; college graduate) compared with other TS/SCPs. CONCLUSION: The existing TS/SCP templates used by US cancer centers are written at a grade level beyond the comprehension of most adults. Cancer care teams should assess TS/SCP content for readability and use of plain language and reduce medical jargon.

Primary care physician's confidence and coordination regarding the survivorship care for older breast cancer survivors.

PURPOSE: To examine primary care physician's (PCPs) internal (confidence, training) and external (communication, receipt of survivorship care plans (SCPs)) regarding their provision of survivorship care to older breast cancer survivors METHOD: A web-based questionnaire was completed individually by PCPs about their training and areas of survivorship they address under their care. A subset of survey participants was interviewed about survivorship care for older breast cancer survivors, care coordination, and areas of improvement regarding SCPs. RESULTS: PCPs (n = 29) had an average 13.5 years in family practice. Forty-five percent surveyed as "somewhat confident" or "not confident" evaluating and managing the late effects of cancer treatment, and 25% surveyed as "somewhat confident" or "not confident" addressing the chronic comorbidities of older breast cancer survivors. More than half of PCPs surveyed that they reach out to their patients' oncologist "a little" or "none of the time" and that they receive SCPs "a little" or "none of the time." Semi-structured interviews also indicated that many PCPs did not receive a SCP from their patients' oncologists and that communication between the two providers regarding survivorship care was poor. CONCLUSION: Participants indicated that PCP confidence in providing survivorship care is lacking and that lack of training, infrequent communication with oncologists, and underutilization of SCPs may contribute to this lack of confidence. These findings provide insight into the possible need for a well-defined shared care model, which has been encouraged but not always a routine part of survivorship care in various practice settings.

Palliative Care Referral Patterns for Adolescent and Young Adult Patients at a Comprehensive Cancer Center.

Palliative care (PC) serves a valuable role throughout the disease trajectory for adolescents and young adults (AYAs) living with cancer. A 3-year retrospective chart review was performed to characterize AYA PC referral patterns in patients aged 18-39 years to identify strategies for improving PC access. Despite known benefits, AYA referrals to PC during oncologic treatment occurred only for a small percentage of eligible patients (8.4%), largely occurred in the inpatient setting (73%), and were more likely in specific cancer types with high symptom burden and/or poor survival, with the greatest penetrance noted in lung cancer (51%).

Advances and future directions in the use of mobile health in supportive cancer care: proceedings of the 2019 MASCC Annual Meeting symposium.

PURPOSE: The role of mobile health (mHealth) technology in cancer care has evolved alongside the rapid development in digital technology. Its use can come with significant potential benefits; however, such use may also be associated with risks. This paper summarizes the latest developments around mHealth use in cancer care presented by a panel of experts at the 2019 Annual Meeting of the Multinational Association of Supportive Care in Cancer. METHODS: Through lectures, case studies, and panel discussions, speakers and participants (including cancer specialist doctors, nurses, and allied health professionals) evaluated current and emerging mHealth methods for supportive care in cancer survivorship. Focus areas and special considerations were agreed upon by consensus. RESULTS: Three focus areas for the use of mHealth in cancer care were identified: activation and support of self-management, exercise oncology, and enablement of survivorship care delivery. In addition to these focus areas, two special considerations were highlighted: technology-enhanced supportive cancer care for disparate populations, and ethical considerations relevant to the use of technology in supportive care. CONCLUSION: mHealth has the potential to revolutionize and transform cancer care delivery. Future research should guide further advances in the use of technology in supportive cancer care and carefully explore the safety, efficacy, cost-effectiveness, and implementation of interventions delivered through mHealth platforms.

Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].

Primary care physicians' perspectives of the survivorship care for older breast cancer survivors: a pilot study.

PURPOSE: To evaluate primary care physicians' (PCPs) role in survivorship care of older breast cancer survivors, their experiences and opinions of survivorship care plans (SCPs), and suggestions for improving care coordination and facilitation of SCPs among older (≥ 65 years) breast cancer survivors. METHODS: A web-based questionnaire was completed individually by PCPs about their training and what areas of survivorship they address under their care. A subset of survey participants were interviewed about survivorship care, care coordination, and the appropriateness and effects of SCPs on older breast cancer survivors' outcomes. RESULTS: Physician participants (N = 29) had an average of 13.5 years in practice. PCPs surveyed that their main role was to provide general health promotion and their least common role was to manage late- and/or long-term effects. Semi-structured interviews indicated that the majority of PCPs did not receive a SCP from their patients' oncologists and that communication regarding survivorship care was poor. Participants' suggestions for improvements to SCPs and survivorship care included regular communication with oncologists, delegation from oncologists regarding roles, and mutual understanding of each other's roles. CONCLUSION: PCPs indicated that survivorship care and SCPs should be improved, regarding communication and roles related to their patients' survivorship. PCPs should assume an active role to enhance PCP-oncologist communication. Future research in PCPs' role in survivorship care in a broad, diverse cancer survivor population is warranted. IMPLICATIONS FOR CANCER SURVIVORS: More attention needs to focus on the importance of PCPs, as they are an integral part of dual management for older breast cancer survivors post-treatment.

Survivorship Fellowship: Evaluation and Evolution of a Program for Advanced Practice Providers.

A comprehensive cancer center in the midwestern United States implemented a stakeholder-engaged quality improvement process to extend its existing one-year advanced practice provider (APP) fellowship program consisting of general oncology education and clinical experience to include an additional survivorship clinical rotation. APP fellowship alumni and program stakeholders reported noticeable benefits and greater importance attributed to program participation, validating inclusion of a survivorship clinic rotation as part of the fellowship program.

Utilization of an audit tool to evaluate accuracy of treatment summary and survivorship care plans.

PURPOSE: A quality review process was implemented to determine compliance with the requirement from the Commission on Cancer to use the American Society of Clinical Oncology (ASCO) template as the minimum data set for Treatment Summary and Survivorship Care Plans (TS/SCP) provided to cancer survivors. METHODS: TS/SCPs generated during 2017 (N = 1257) were audited for concordance with each of the 66 TS/SCP line items on ASCO's template. Descriptive statistics and chi-square statistics were used to examine line item concordance, overall and by services groups (survivorship vs. other oncology service). Mixed-effects logistic regression was used to estimate the effects of service delivery group on the concordance. RESULTS: Institutional compliance with the ASCO template was very high; 76% of the 66 line items were present in at least 75% of the delivered TS/SCPs. There was a significantly higher rate of concordance for TS/SCPs provided by the survivorship service (83% vs. 66%, P = 0.006). TS/SCPs provided by the survivorship service were nearly twice as likely to be concordant with ASCO template (OR = 1.88, 95% CI = 1.77-2.00) compared to those by other service groups. CONCLUSIONS: Use of the electronic medical record to auto-populate information was instrumental in achieving a high rate of concordance. Institutions should consider providing training to improve or maintain quality of these documents. IMPLICATIONS FOR CANCER SURVIVORS: Ensuring that the information contained on the TS/SCP is consistently present is necessary for a high-quality survivorship visit between the clinician, PCP, and survivor and as a record of care for future health care encounters.

Survivorship care plan preferences of cancer survivors and health care providers: a systematic review and quality appraisal of the evidence.

PURPOSE: The purpose of this systematic review was to describe and examine the current use of treatment summaries and survivorship care plans (TSs/SCPs) for cancer survivors, as well as to summarize and critically assess relevant literature regarding their preferences and usefulness. There is a knowledge gap regarding the preferences of stakeholders as to what is useful on a treatment summary or survivorship care plan. METHODS: A systematic review of eligible manuscripts was conducted using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Relevant studies were identified via PubMed, CINAHL Plus, and the Cochrane Library from 2005 through 2013. Eligible studies were critically appraised with qualitative and quantitative appraisal tools. RESULTS: There were 29 studies included in this review; 19 were quantitative. Survivors and primary care physicians preferred a printable format delivered 0 to 6 months posttreatment and highlighting signs and symptoms of recurrence, late, and long-term effects, and recommendations for healthy living. Oncology providers supported the concept of treatment summary and survivorship care plan but reported significant barriers to their provision. No studies incorporated caregiver perspectives of treatment summary and survivorship care plan. CONCLUSION: This systematic review did not reveal conclusive evidence regarding the needs of survivors or providers regarding treatment summaries and survivorship care plans. A lack of rigorous studies contributed to this. IMPLICATIONS FOR CANCER SURVIVORS: Treatment summaries and survivorship care plans are useful for cancer survivors; however, future rigorous studies should be conducted to identify and prioritize the preferences of survivors regarding these.

Extrahepatic disease should not preclude transarterial chemoembolization for metastatic neuroendocrine carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is often utilized for patients with inoperable neuroendocrine carcinoma liver metastases. Often, metastatic disease is not limited to the liver. The impact of extrahepatic disease (EHD) on outcomes and response after TACE has not been described. METHODS: We reviewed 192 patients who underwent TACE for large hepatic tumor burden, progression of liver metastases, or poorly controlled carcinoid syndrome due to neuroendocrine carcinoma. Demographics, clinicopathologic characteristics, response to TACE, complications, and survival were compared between patients with (n = 123) and without (n = 69) EHD. RESULTS: Demographics, histopathologic characteristics, and complications were similar between groups. As well, those with and without EHD had similar biochemical (85 vs. 88 %) and radiographic response (76 vs. 79 %) to TACE (all p = NS); however, symptomatic responses were improved in those with EHD (79 vs. 60 %, p = 0.01). The group without EHD had better overall survival compared to those with EHD disease at the time of TACE (median 62 vs. 28 months, p = 0.001). DISCUSSION: Although patients with EHD from neuroendocrine carcinoma experience shorter overall survival after TACE compared to those without EHD, they had similar symptomatic, biochemical, and radiographic response to TACE. Meaningful response to TACE is still possible in the presence of EHD and should be considered, particularly in those with carcinoid syndrome.

A scoring system for the prognosis and treatment of malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction is a common result of end-stage abdominal cancer that is a treatment dilemma for many physicians. Little has been reported predicting outcomes or determining the role of surgical intervention. We sought to review our experience with surgical and nonsurgical management of malignant bowel obstruction to identify predictors of 30-day mortality and of who would most likely benefit from surgical intervention. METHODS: A chart review of 523 patients treated between 2000 and 2007 with malignant bowel obstruction were evaluated for factors present at admission to determine return to oral intake, 30-day mortality, and overall survival. Propensity score matching was used to homogenize patients treated with and without surgery to identify those who would benefit most from operative intervention. RESULTS: Radiographic evidence of large bowel obstruction was predictive of return to oral intake. Hypoalbuminemia and radiographic evidence of ascites or carcinomatosis were all predictive of increased 30-day mortality and overall survival. A nomogram of 5 identified risk factors correlated with increased 30-day mortality independent of therapy. Patients with large bowel or partial small bowel obstruction benefited most from surgery. A second nomogram was created from 4 identified risk factors that revealed which patients with complete small bowel obstruction might benefit from surgery. CONCLUSION: Two nomograms were created that may guide decisions in the care of patients with malignant bowel obstruction. These nomograms are able to predict 30-day mortality and who may benefit from surgery for small bowel obstruction.

Cytopathologic evaluation of the in situ margin in patients undergoing hepatectomy.

BACKGROUND: Margin status is a predictor of outcome for patients with liver malignancies, although what constitutes a negative margin is controversial. Traditionally, the completeness of resection is estimated by surgical histopathology of the resected specimen margin, despite the in situ margin being potentially more important. The true margin is often altered by parenchymal transection techniques. The authors propose that cytologic assessment of the in situ margin is more specific for determining the true margin. METHODS: A total of 84 patients with primary or metastatic liver tumors who were undergoing surgical resection were enrolled in this prospective Institutional Review Board-approved study. Specimen and in situ (patient) margins were assessed using a "scrape preparation" cytologic technique and compared with traditional surgical histopathology. Patients were followed for assessment of local disease recurrence. RESULTS: Follow-up data were complete for 64 patients for a median of 37 months (range, 12 months-56 months). Twenty patients were excluded because of perioperative death (6 patients; 7%) or a follow-up of < 12 months. Seven patients (12.2%) had positive histopathologic specimen margins, but only 1 was found to be positive by cytology (1.8%). No in situ cytologically positive margins were identified along the cut edge of the liver remnant. The rate of intra- or extrahepatic recurrences was 56.7%, whereas the local recurrence rate was 1.8%. One patient with local recurrence demonstrated simultaneous intra- and extrahepatic disease recurrences and had negative margins by all methods of evaluation. CONCLUSIONS: To the authors' knowledge, the current study is the first to demonstrate that in situ margins can be assessed using cytopathology. This method is quick and can be universally applied. Given the difficulty of accurately assessing margins after hepatectomy, cytopathologic evaluation may be more reflective of the true margin. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.

Pancreatic resection in the octogenarian: a safe option for pancreatic malignancy.

BACKGROUND: The incidence of pancreatic cancer is age related; patients older than the age of 65 represent 60% of all cases. We assessed our institution's experience and outcomes with pancreatic resection for malignancy in patients in their ninth decade. STUDY DESIGN: We reviewed records of patients undergoing pancreatic resection for malignancy at our institution between 1990 and 2007. Demographics, laboratory, treatment, and outcomes data were gathered. Comparisons were made between patients older and younger than the age of 80. Survival was analyzed using the Kaplan-Meier method and comparisons between groups were performed using the log-rank test. Regression methods were used to evaluate predictors of outcomes. RESULTS: There were 517 pancreatic resections for cancer reviewed. Of these, 27 patients were 80 years or older (age range 80 to 91 years), compared with 490 patients less than 80 (range 20 to 79 years). The distribution of clinical characteristics was similar between the 2 groups. The majority of patients undergoing pancreatic resection harbored a mass in the head of the pancreas, so the most common procedure was pancreaticoduodenectomy (n = 398, 78%). There were no significant differences in complication rates for younger and older groups (59% vs 52%, respectively, p = 0.4), median length of stay (11 vs 12 days, p = 0.33), or perioperative mortality rates (3.7% vs 3.7%, p = 1.0). Overall survival between the 2 groups was similar (21.9 vs 33.3 months, p = 0.18). CONCLUSIONS: Pancreatectomy for malignancy is a safe option for the elderly. Patients older than age 80 achieved similar results, with similar rates of perioperative complications and mortality. Pancreatectomy for cancer offers a similar survival benefit in both groups.

Failure of normalization of CA19-9 following resection for pancreatic cancer is tantamount to metastatic disease.

BACKGROUND: Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabine-based chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease. METHODS: From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student's t-test and contingency table analyses. Survival curves were constructed using Kaplan-Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival. RESULTS: The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p < 0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002]. CONCLUSIONS: Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.

Repeat transarterial chemoembolization (TACE) for progressive hepatic carcinoid metastases provides results similar to first TACE.

BACKGROUND: Transarterial chemoembolization (TACE) is commonly used to treat metastatic carcinoid tumors; however, the management of progressive disease is less clear. We sought to determine if patients with disease progression after TACE would benefit from repeat TACE. METHODS: The records of 27 patients undergoing repeat TACE for radiologic or symptomatic progression after TACE for metastatic carcinoid were reviewed and compared to 122 undergoing first TACE. Overall and progression-free survivals were estimated by the Kaplan-Meier method. RESULTS: Mean disease-free interval after first TACE was 11.8 months. Radiologic response was observed in 61% compared to 82% after first TACE (p=0.058); hormone response in 64% compared to 80% (p=0.159); and symptomatic response in 77% compared to 92% (p=0.053). The complication rate after repeat TACE was lower than after first TACE (p=0.03). Median overall survival was similar after repeat (28.1 months) and first TACE (33.3 months) (p=0.53). Progression-free survival was shorter after repeat TACE but not significantly so. No factor examined could predict survival after repeat TACE. CONCLUSION: Repeat TACE for patients with hepatic carcinoid metastases failing first TACE or having evidence of disease progression is safe and offers a viable treatment option.

Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned.

BACKGROUND: Hepatic artery chemoembolization (HACE) is a treatment option in the management of metastatic carcinoid. We reviewed our experience to identify potential factors that influence survival. METHODS: The records of 122 patients with metastatic carcinoid tumor undergoing HACE were reviewed. Log-rank analysis and Cox proportional hazards were applied to identify factors predictive of decreased survival. RESULTS: Median follow-up after HACE was 21.5 months. Complications occurred in 23% with periprocedural mortality of 5%. Radiographic tumor regression was seen in 82%, with stabilization of disease in 12%. Median duration of CT response was 19 months. Improvement in symptoms occurred in 92% for median duration of 13 months. HACE resulted in complete normalization of serum pancreastatin in 14%, with greater than 20% reduction in another 66%. Median overall survival was 33.3 months after HACE. Only pancreastatin level > or =5,000 pg/ml was associated with decreased survival by multivariate analysis. CONCLUSION: HACE offers symptom palliation and long-term survival in patients with incurable carcinoid metastases. Although safe, it should be approached cautiously in patients with significant tumor burden as evidenced by pancreastatin levels > or =5,000 pg/ml. We do not recommend whole-liver embolization in these patients but prefer a staged approach to each lobe of the liver.

Genetic fate of recombinant adeno-associated virus vector genomes in muscle.

Recombinant adeno-associated virus (rAAV) vectors are promising human gene transfer vectors, because they mediate long-term gene expression in vivo. The vector DNA form responsible for sustained gene expression has not been clearly defined, but it has been presumed that the vector integrates to some degree and persists in this manner. Using two independent methods, we were unable to identify rAAV integrants in mouse muscle. In the first approach, we were unable to recover host cell-vector DNA junctions from a lambda phage library generated using transduced mouse muscle DNA that contained a high vector copy number. Following this result, we devised a PCR assay based on the principle that integrated rAAV vector sequences could be amplified using primers specific for mouse interspersed repetitive sequences (B1 elements). Using this assay, we analyzed transduced mouse muscle DNA isolated from 6 to 57 weeks after injection and did not detect amplification above background levels. Based on the demonstrated sensitivity of the assay, these results suggested that >99.5% of vector DNA was not integrated. Additional analyses using a novel DNA exonuclease showed that the majority of the rAAV vector DNA in muscle persisted over time as transcriptionally active monomeric and concatameric episomes.