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Full-thickness rotator cuff tears (FTRCTs) represent a common shoulder injury that, if untreated, can progress in size, become increasingly painful, and inhibit function. These lesions are often surgically repaired, with double-row arthroscopic repair often preferred for larger tears. Biological augmentation technologies have been developed to improve rates of postoperative radiographic retear and enhance patient-reported outcomes after surgical FTRCT repair. This study sought to confirm that augmented repair with a bioinductive bovine collagen implant results in favorable retear rates and patient outcomes with follow-up to 2 years.A prospective multicenter cohort study was undertaken to determine the efficacy and safety of augmenting single- or double-row arthroscopic repair of FTRCTs with a bioinductive bovine collagen implant. Of 115 adult patients participating, 66 (57.4%) had medium (1-3-cm) tears and 49 (42.6%) had large (3-5-cm) tears. Magnetic resonance imaging and patient-reported outcomes (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form [ASES] and Constant-Murley Score [CMS]) were performed and recorded at baseline, 3 months, 1 year, and 2 years.Mean duration of follow-up was 2.1 years (range, 1.5-2.9 years). Between baseline and 2-year follow-up, mean total thickness of the supraspinatus tendon increased by 12.5% for medium tears and by 17.1% for large tears. Radiographic retear was noted in 7 of 61 available patients (11.5%) with medium tears, and in 14 of 40 patients (35.0%) with large tears. In both groups, these tears primarily occurred before the 3-month follow-up visit (13 of 21 [61.9%]). Radiographic retear with the supplemented double-row (DR) repair technique was 13.2% overall (12 of 91 DR patients; 11.3% for medium tears and 15.8% for large tears). The minimal clinically important difference was achieved by90% of patients with both medium and large tears for both ASES and CMS. There were 2 serious adverse events classified by the treating surgeon as being possibly related to the device and/or procedure (1 case of swelling/drainage and 1 case of intermittent pain). Nine patients (7.8%; 4 medium tears and 5 large tears) required reoperation of the index rotator cuff surgery.Final 2-year data from this study confirm that using this implant in augmentation of arthroscopic double-row repair of FTRCTs provides favorable rates of radiographic retear and substantial functional recovery. The relative safety of the device is also further supported.

PURPOSE The National Cancer Institute–Children's Oncology Group Pediatric MATCH trial aimed to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations. PATIENTS AND METHODS Tumors from patients age 1-21 years with refractory solid tumors, lymphomas, or histiocytic disorders were subjected to cancer gene panel sequencing and limited immunohistochemistry to identify actionable alterations for assignment to phase II treatment arms. The rates of treatment arm assignment and enrollment were compared between clinical and demographic groups. RESULTS Testing was completed for 94.7% of tumors submitted. Actionable alterations were detected in 31.5% of the first 1,000 tumors screened, with treatment arm assignment and enrollment occurring in 28.4% and 13.1% of patients, respectively. Assignment rates varied by tumor histology and were higher for patients with CNS tumors or enrolled at Pediatric Early Phase Clinical Trials Network sites. A reported history of prior clinical molecular testing was associated with higher assignment and enrollment rates. Actionable alterations in the mitogen-activated protein kinase signaling pathway were most frequent (11.2%). The most common reasons provided for not enrolling on treatment arms were patients receiving other treatment or poor clinical status. CONCLUSION The Pediatric MATCH trial has proven the feasibility of a nationwide screening Protocol for identification of actionable genetic alterations and assignment of pediatric and young adult patients with refractory cancers to trials of molecularly targeted therapies. These data support the early use of tumor molecular screening for childhood patients with cancer whose tumors have not responded to standard treatments.

Background Current surgical treatment options for partial-thickness tears (eg, takedown and repair, in situ repair) are limited by the degenerative nature of the underlying tendon and may require extensive intervention that can alter the anatomic footprint. The complexity of available techniques to address these issues led to the development of a resorbable collagen implant, which can be used to create a bioinductive repair of partial-thickness tears. Methods We prospectively enrolled 33 patients with chronic, degenerative, intermediate-grade (n = 12), or high-grade (n = 21) partial-thickness tears (11 articular, 10 bursal, 4 intrasubstance, and 8 hybrid) of the supraspinatus tendon in a multicenter study. After arthroscopic subacromial decompression without a traditional rotator cuff repair, a bioinductive implant was secured over the bursal surface of the tendon. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons (ASES) and Constant-Murley scores (CMS) preoperatively and at 3 months, 1 year, and 2 years postoperatively. Magnetic resonance imaging was performed to assess postoperative tendon healing and thickness at the original tear site. Results At 2-year follow-up, mean ASES and CMS scores improved both clinically and statistically at 1 and 2 years, compared with baseline, for intermediate- and high-grade tears. There was magnetic resonance imaging evidence of new tissue fill-in within the original baseline tear in 100% of the intermediate-grade tears and 95% of the high-grade tears. In 90.9% of the intermediate-grade tears and 84.2% of the high-grade tears, this new tissue fill-in represented at least an additional 50% of the volume of the initial lesion. From baseline to 2-year follow-up, the mean tendon thickness increased by 1.2 mm (standard deviation, 1.3; P = .012) and 1.8 mm (standard deviation, 2.2; P = .003) in the intermediate- and high-grade tears, respectively. The analysis of tear grade and location revealed no statistically significant difference in the change in mean tendon thickness at any time point. One patient with a high-grade articular lesion demonstrated progression to a full-thickness tear; however, the patient was noncompliant and the injury occurred while shoveling snow 1 month after surgery. Neither tear location nor treatment of bicep pathology affected the ASES or CMS scores at any follow-up point. No serious adverse events related to the implant were reported. Conclusion Final results from this 2-year prospective study indicate that the use of this resorbable bovine collagen implant for isolated bioinductive repair of intermediate- and high-grade partial-thickness rotator cuff tears of the supraspinatus is safe and effective, regardless of tear grade and location.

Background: Biologic technologies can potentially augment existing arthroscopic rotator cuff repair to improve retear rates and postoperative outcomes. The purpose of this study was to evaluate healing rates and clinical outcomes of full-thickness rotator cuff repairs augmented with a bioinductive bovine collagen implant. Methods: In this prospective multicenter study, investigators enrolled 115 patients (mean age, 60.4 years) with full-thickness rotator cuff tears. There were 66 (57.4%) medium (1-3 cm) tears and 49 (42.6%) large (3-5 cm) tears. Eligible patients consisted of those ≥21 years of age with chronic shoulder pain lasting longer than 3 months and unresponsive to conservative therapy. Patients underwent single- or double-row repair augmented with a bioinductive bovine collagen implant. At the baseline, 3 months, and 1 year, magnetic resonance imaging was performed and patients were assessed for American Shoulder and Elbow Surgeons (ASES) Shoulder Score and Constant-Murley Score (CMS). The primary failure end point was retear, classified as any new full-thickness defect observed on magnetic resonance imaging. Results: There were 13 retears (11.3%) at 3 months, with an additional 6 (19 total [16.5%]) found at 1 year. In large tears, double-row repair had a significantly lower rate of retear at 3 months (P = .0004) and 1 year (P = .0001) compared with single-row repair. ASES and CMS scores significantly improved between the baseline and 1 year for medium and large tears. At 1 year, the minimally clinically important difference for ASES and CMS was met by 91.7% (95% CI: 84.9-96.1) and 86.4% (95% CI: 78.2-92.4) of patients, respectively. Patients without retear and those

The optimal surgical approach for recurrent anterior shoulder instability remains controversial, particularly in the face of glenoid and/or humeral bone loss. The purpose of this study was to use a contingent-behavior questionnaire (CBQ) to determine which factors drive surgeons to perform bony procedures over soft tissue procedures to address recurrent anterior shoulder instability.A CBQ survey presented each respondent with 32 clinical vignettes of recurrent shoulder instability that contained 8 patient factors. The factors included (1) age, (2) sex, (3) hand dominance, (4) number of previous dislocations, (5) activity level, (6) generalized laxity, (7) glenoid bone loss, and (8) glenoid track. The survey was distributed to fellowship-trained surgeons in shoulder/elbow or sports medicine. Respondents were asked to recommend either a soft tissue or bone-based procedure, then specifically recommend a type of procedure. Responses were analyzed using a multinomial-logit regression model that quantified the relative importance of the patient characteristics in choosing bony procedures.Seventy orthopedic surgeons completed the survey, 33 were shoulder/elbow fellowship trained and 37 were sports medicine fellowship trained; 52% were in clinical practice ≥10 years and 48%10 years; and 95% reported that the shoulder surgery made up at least 25% of their practice. There were 53% from private practice, 33% from academic medicine, and 14% in government settings. Amount of glenoid bone loss was the single most important factor driving surgeons to perform bony procedures over soft tissue procedures, followed by the patient age (19-25 years) and the patient activity level. The number of prior dislocations and glenoid track status did not have a strong influence on respondents' decision making. Twenty-one percent glenoid bone loss was the threshold of bone loss that influenced decision toward a bony procedure. If surgeons performed 10 or more open procedures per year, they were more likely to perform a bony procedure.The factors that drove surgeons to choose bony procedures were the amount of glenoid bone loss with the threshold at 21%, patient age, and their activity demands. Surprisingly, glenoid track status and the number of previous dislocations did not strongly influence surgical treatment decisions. Ten open shoulder procedures a year seems to provide a level of comfort to recommend bony treatment for shoulder instability.

PURPOSE Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols. PATIENTS AND METHODS Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with NGS and selected immunohistochemistry in a master screening protocol. The treatment-assignment rate to treatment arms was assessed. Molecular alterations in seven tumors profiled in both NCI-MATCH trial and The Cancer Genome Atlas (TCGA) of primary tumors were compared. RESULTS Molecular profiling was successful in 93.0% of specimens. An actionable alteration was found in 37.6%. After applying clinical and molecular exclusion criteria, 17.8% were assigned (26.4% could have been assigned if all subprotocols were available simultaneously). Eleven subprotocols reached their accrual goal as of this report. Actionability rates differed among histologies (eg, > 35% for urothelial cancers and < 6% for pancreatic and small-cell lung cancer). Multiple actionable or resistance-conferring tumor mutations were seen in 11.9% and 71.3% of specimens, respectively. Known resistance mutations to targeted therapies were numerically more frequent in NCI-MATCH than TCGA tumors, but not markedly so. CONCLUSION We demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted-therapy regimens.

Purpose The purpose of this study was to perform a Delphi consensus for the treatment of patients with shoulder impingement with intact rotator cuff tendons, comparing North American to European shoulder surgeon preferences. Methods Nineteen surgeons from North America [NAP] and 18 surgeons from Europe [EP] agreed to participate and answered 10 open-ended questions in rounds 1 and 2. The results of the first two rounds were used to develop a Likert style questionnaire for round 3. If agreement at round 3 was 60% for an item, the results were carried forward into round 4. For round 4 the panel members outside consensus >60%, Results There was agreement on the following items: impingement is a clinical diagnosis; a combination of clinical tests should be used; other pain generators must be excluded; radiographs must be part of the work up; MR imaging is helpful; the first line of treatment should always be physiotherapy; a corticosteroid injection is helpful in reducing symptoms; indication for surgery is failure of non-operative treatment for a minimum of 6 months. The NAP were likely to routinely prescribe NSAIDs [NA 89%; EU 35%] and consider steroids for impingement [NA 89%. EU 65%]. Conclusion Consensus was achieved for 16 of the 71 Likert items: impingement is a clinical diagnosis and a combination of clinical tests should be used. The first line of treatment should always be physiotherapy, and a corticosteroid injection can be helpful in reducing symptoms. The indication for surgery is failure of non-operative treatment for a minimum of 6 months. The panel also agreed that SAD is a good choice for shoulder impingement if there is evidence of mechanical impingement with pain not responding to non-surgical measures.

PURPOSE The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (> 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti–programmed death receptor 1 inhibitor nivolumab previously showed activity in mismatch repair (MMR)–deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors. PATIENTS AND METHODS Eligible patients with relapsed or refractory tumors, good end-organ function, and Eastern Cooperative Oncology Group performance status of ≤ 1 underwent tumor biopsy for centralized screening of molecular alterations. MMR deficiency was defined by complete loss of nuclear expression of MLH1 or MSH2 MMR gene products by immunohistochemistry (IHC). Patients with MMR-deficient colorectal cancer were excluded. Nivolumab, 3 mg/kg every 2 weeks (28-day cycles) and 480 mg every 4 weeks after cycle 4, was administered intravenously. Disease reassessment was performed every 2 cycles. The primary end point was RECIST 1.1 objective response rate (ORR). RESULTS Two percent of 4,902 screened patients had an MMR-deficient cancer by IHC. Forty-two evaluable patients were enrolled, with a median age of 60 years and a median of 3 prior therapies. The most common histologies were endometrioid endometrial adenocarcinoma (n = 13), prostate adenocarcinoma (n = 5), and uterine carcinosarcoma (n = 4). ORR was 36% (15 of 42 patients). An additional 21% of patients had stable disease. The estimated 6-, 12-, and 18-month progression-free survival rates were 51.3% (90% CI, 38.2% to 64.5%), 46.2% (90% CI, 33.1% to 59.3%), and 31.4% (90% CI, 18.7% to 44.2%), respectively. Median overall survival was 17.3 months. Toxicity was predominantly low grade. CONCLUSION A variety of refractory cancers (2.0% of those screened) had MMR deficiency as defined in NCI-MATCH. Nivolumab has promising activity in MMR-deficient noncolorectal cancers of a wide variety of histopathologic types.

Early drug development for cancer requires broad collaboration and skilled clinical investigators to enable enrollment of patients whose tumors have defined molecular profiles. To respond to these challenges, the National Cancer Institute (NCI) transformed its 60-year-old early-phase drug development program in 2014 into the Experimental Therapeutics Clinical Trials Network (ETCTN). The ETCTN is a consolidated, national network of 40+ academic institutions responsible for conducting more than 100 early-phase clinical trials. It promotes team science coordinated among basic, translational, and clinical investigators, emphasizing the inclusion of early career trialists. This perspective provides a brief overview of the ETCTN, summarizes its successes and challenges over its first grant funding cycle, and discusses the program's future directions. Measures indicated strong connectivity across the institutions, significant increases in investigator approval of the ETCTN scientific portfolio from years 1 to 4, and substantial research activity over 5 years, with 334 letters of intent submitted, 102 trials activated, and 3,570 patients accrued. The ETCTN's successful adoption relied heavily on the inclusion of senior investigators who have long-standing interactions with the NCI and a willingness to participate in a team science approach and to mentor early career investigators. In addition, NCI invested substantial resources in a centralized infrastructure to conduct trials and to support the inclusion of biomarkers in its studies. The ETCTN provides evidence that a collaborative national clinical trial network for early drug development is feasible and can address the demands of precision medicine approaches to oncologic clinical trials.

Background Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer. Methods Patients with stage I–III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided. Results A total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%). Conclusions We found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.

Purpose: Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories. Experimental Design: To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH. Results: The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data. Conclusions: This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.

Background: Black race is associated with worse outcomes in localized hormone receptor (HR)-positive breast cancer in population-based and in clinical trial cohorts, whether using self-identified race (Albain et al. JNCI 2009 [PMID: 19584328; Sparano et al. JNCI 2012 [PMID: 22250182) or genetically-identified race (Schneider et al. J Precision Oncol 2017 [PMID: 29333527]). This disparity persists after adjustment for treatment delivery parameters (Hershman et al. JCO 2009 [PMID:19307504]). We evaluated clinicopathologic characteristics, treatment delivered and clinical outcomes in the Trial Assigning Individualized Options for Treatment (TAILORx) by race and ethnicity (Sparano et al. NEJM 2018 [PMID: 29860917]). Methods: The analysis included 9719 evaluable TAILORx participants. The association between clinical outcomes and race (white, black, Asian, other/unknown) and ethnicity (Hispanic vs. non-Hispanic) was examined, including invasive disease-free survival (iDFS), distant relapse-free interval (DRFI), relapse-free interval (RFI), and overall survival (OS). Proportional hazards models were fit including age (5 categories), tumor size (>2 cm vs. Results: The study population included 8189 (84%) whites, 693 (7%) blacks, 405 (4%) Asians, and 432 (4%) with other/unknown race. Regarding ethnicity, 7635 (79%) were non-Hispanic, 889 (9%) Hispanic, and 1195 (12%) unknown. There was no significant difference in RS distribution (p=0.22) in blacks compared with whites, or in median (17 vs. 17) or mean RS (19.1 vs. 18.2). There was likewise no difference in Hispanic vs. non-Hispanic ethnicity for RS distribution (p=0.72) or median (17 vs. 17) or mean RS (18.5 vs. 18.0). Black race (39% vs. 30%) and Hispanic ethnicity (39% vs. 30%) were both associated with younger age ( Race (black vs.white) and clinical outcomes in proportional hazards modelsClinical endpointEntire Population (N=693 black) Hazard ratio for eventRS 11-25 (N=471 black) Hazard ratio for eveniDFS1.33 (p=0.005)1.49 (p=0.001)DRFI1.21 (p=0.28)1.60 (p=0.02)RFI1.39 (p=0.02)1.80 (p Conclusions: In patients eligible and selected for participation in TAILORx, black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy. This adds to an emerging body of evidence suggesting a biologic basis or other factors contributing to racial disparities in HR-positive breast cancer that requires further evaluation. Citation Format: Albain K, Gray RJ, Sparano JA, Makower DF, Pritchard KI, Hayes DF, Geyer, Jr. CE, Dees EC, Goetz MP, Olson, Jr. JA, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge, Jr. GW. Race, ethnicity and clinical outcomes in hormone receptor-positive, HER2-negative, node-negative breast cancer: results from the TAILORx trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-07.

Background Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results Of 9719 eligible women with hormone receptor–positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.

Superior capsular reconstruction is a powerful tool for the treatment of massive irreparable rotator cuff tears. Several authors have described this evolving technique. Issues of graft sizing, graft passage, graft tensioning, and suture management make this a challenging procedure even in the hands of experienced shoulder surgeons. We describe our arthroscopic technique for superior capsular reconstruction using nonirradiated human acellular dermis. We introduce several techniques for graft passage and tensioning that may help to simplify this challenging procedure and make it more reproducible.

The National Institutes of Health (NIH) issued a new policy that requires a single institutional review board (IRB) of record be used for all protocols funded by the NIH that are carried out at more than one site in the United States, effective January 2018. This policy affects several hundred clinical trials opened annually across the NIH. Limited data exist to compare the use of a single IRB to that of multiple local IRBs, so some institutions are resistant to or distrustful of single IRBs. Since 2001, the National Cancer Institute (NCI) has funded a central IRB (CIRB) that provides human patient reviews for its extensive national cancer clinical trials program. This paper presents data to show the adoption, efficiencies gained, and satisfaction of the CIRB among NCI trial networks and reviews key lessons gleaned from 16 years of experience that may be informative for others charged with implementation of the new NIH single-IRB policy.

Objective: To present recommendations for the diagnosis, management, outcomes, and return to play of athletes with superior labral anterior-posterior (SLAP) injuries. Background: In overhead athletes, SLAP tears are common as either acute or chronic injuries. The clinical guidelines presented here were developed based on a systematic review of the current evidence and the consensus of the writing panel. Clinicians can use these guidelines to inform decision making regarding the diagnosis, acute and long-term conservative and surgical treatment, and expected outcomes of and return-to-play guidelines for athletes with SLAP injuries. Recommendations: Physical examination tests may aid diagnosis; 6 tests are recommended for confirming and 1 test is recommended for ruling out a SLAP lesion. Combinations of tests may be helpful to diagnose SLAP lesions. Clinical trials directly comparing outcomes between surgical and nonoperative management are absent; however, in cohort trials, the reports of function and return-to-sport outcomes are similar for each management approach. Nonoperative management that includes rehabilitation, nonsteroidal anti-inflammatory drugs, and corticosteroid injections is recommended as the first line of treatment. Rehabilitation should address deficits in shoulder internal rotation, total arc of motion, and horizontal-adduction motion, as well as periscapular and glenohumeral muscle strength, endurance, and neuromuscular control. Most researchers have examined the outcomes of surgical management and found high levels of satisfaction and return of shoulder function, but the ability to return to sport varied widely, with 20% to 94% of patients returning to their sport after surgical or nonoperative management. On average, 55% of athletes returned to full participation in prior sports, but overhead athletes had a lower average return of 45%. Additional work is needed to define the criteria for diagnosing and guiding clinical decision making to optimize outcomes and return to play.

Cancer clinical trials provide the evidence on which sound oncology practice is based. Assuring rapid enrollment to clinical trials is a major goal of all sponsors and funders and depends to a great extent on the efficiency of the infrastructure that supports this research. Increasingly, National Cancer Institute- and biopharmaceutical-sponsored trials encourage the participation of physicians engaged in community practice, in addition to the more traditional involvement of academic institutions. The characteristics that ensure quality research in these varied practice settings are reviewed in this chapter and tools that facilitate enrollment are described.

Importance A high 21-gene recurrence score (RS) by breast cancer assay is prognostic for distant recurrence of early breast cancer after local therapy and endocrine therapy alone, and for chemotherapy benefit. Objective To describe clinical outcomes for women with a high RS who received adjuvant chemotherapy plus endocrine therapy in the TAILORx trial, a population expected to have a high distant recurrence rate with endocrine therapy alone. Design, Setting, and Participants In this secondary analysis of data from a multicenter randomized clinical trial, 1389 women with hormone receptor–positive, ERBB2-negative, axillary node-negative breast cancer, and a high RS of 26 to 100 were prospectively assigned to receive adjuvant chemotherapy in addition to endocrine therapy. The analysis was conducted on on May 12, 2019. Interventions The adjuvant chemotherapy regimen was selected by the treating physician. Main Outcomes and Measures Freedom from recurrence of breast cancer at a distant site, and freedom from recurrence, second primary cancer, and death (also known as invasive disease-free survival [IDFS]). Results Among the 9719 eligible women, with a mean age of 56 years (range 23-75 years), 1389 (14%) had a recurrence score of 26 to 100, of whom 598 (42%) had an RS of 26 to 30 and 791 (58%) had an RS of 31 to 100. The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-fluorouracil in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). At 5 years, the estimated rate of freedom from recurrence of breast cancer at a distant site was 93.0% (standard error [SE], 0.8%), freedom of recurrence of breast cancer at a distant and/or local regional site 91.0% (SE, 0.8%), IDFS 87.6% (SE, 1.0%), and overall survival 95.9% (SE, 0.6%). Conclusions and Relevance The estimated rate of freedom from recurrence of breast cancer at a distant site in women with an RS of 26 to 100 treated largely with taxane and/or anthracycline-containing adjuvant chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population. Trial Registration ClinicalTrials.gov identifierNCT00310180

Rotator cuff tears are increasing in frequency in the aging population and are a common issue seen by orthopaedic surgeons. In patients with large, multi-tendon rotator cuff tears or retears, treatment can be challenging. Failure rates of up to 90% have been reported for rotator cuff repair (RCR) of large, multi-tendon tears. Biological augmentation has been an area of interest because of the distinctly different biology of the repaired tendon compared with the native tendon. These biological differences affect the ultimate tensile properties of the repair and may contribute to gap formation and the high failure rate of repairs. RCR with allograft augmentation is a technique that shows potential benefit to healing and preventing retears. Arthroscopic augmentation of RCRs can be challenging. The technique described in this Technical Note illustrates a simple and easily reproducible method for augmenting RCRs with human acellular dermal allograft.

The controversy as to what is the best technique to repair a rotator cuff continues, with single-anchor row versus double-row techniques being highlighted. The literature has presented multiple studies with clinical outcomes being similar, even though double-row linked and transosseous-equivalent repairs have a higher success rate with postoperative imaging. Clinical outcome instruments weigh pain as a major criterion, but strength improvement favors an intact repair. Treatment of chronic rotator cuff tears often yields muscular changes that may compromise the strength-improvement portion of the outcome. Larger tears benefit from additional fixation, and tissue loss continues to require adjustments to the repair strategy. Attempting a repair that emphasizes footprint coverage may over-tension the cuff repair and risk shoulder stiffness and medial failure of the repair. By use of a 3-dimensional spherical attachment surface, a linked infraspinatus repair can be combined with an anteromedial supraspinatus repair to create a lower-tensioned secure repair. Additional grafting methods, including use of the biceps, may provide additional strength to the repair construct.

Surgical repair of shoulder instability is challenging, and multiple procedures have been proposed. In an attempt to reduce risk of recurrence following surgical reconstruction, some surgeons have added steps to prior arthroscopic procedures, and other surgeons have selected a bone reinforcement procedure. These additional augmented repair techniques have reduced the risk of postoperative recurrence, but introduced additional risk of complications related to hardware, fixation, and possible need for additional surgery. Surgeons should become familiar with multiple surgical procedures to treat patients with recurrent shoulder instability, and select the appropriate procedure that addresses the demands of the athlete's shoulder and minimize the risk of complication.

Since 1998, the National Cancer Institute (NCI) has mandated that researchers use its consent form template in developing consent forms for their NCI-funded clinical trials. The template was substantially revised in 2013 to aid in the development of simpler, more concise consent forms. The NCI conducted a randomized controlled trial with cancer survivors (N = 153) to assess the revised template's effect on individuals' knowledge, satisfaction, clarity, and likelihood of joining a trial in the future. We found that the revised template resulted in equally high knowledge and satisfaction scores as the original template, but with fewer words and pages. The likelihood that an individual would participate in a trial diminished after he or she reviewed either the original or revised consent form, yet having knowledge about trials before reviewing the consent forms resulted in increased satisfaction. To ensure an informed decision-making process, we recommend using the revised NCI consent form template along with using educational interventions aimed at increasing the understanding potential participants have of a trial before they receive a consent form.

Contains fulltext : 171566.pdf (Publisher’s version ) (Open Access) The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure).

Treatment of partial-thickness cuff tears remains controversial. Although conservative therapy may treat symptoms, these defects do not spontaneously heal and conversion to a full-thickness lesion with subsequent repair may alter the tendon footprint. The ability to induce new tissue formation and limit tear progression in intermediate- and high-grade partial-thickness tears without surgical repair may represent a significant advancement in the treatment paradigm for these lesions.We prospectively enrolled 33 patients with chronic, degenerative, intermediate-grade (n = 12) or high-grade (n = 21) partial-thickness tears (11 articular, 10 bursal, 4 intrasubstance, and 8 hybrid) of the supraspinatus tendon in a multicenter study. Following arthroscopic subacromial decompression without repair, a bioinductive implant was attached over the bursal surface of the tendon. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons and Constant-Murley scores preoperatively and at 3 and 12 months postoperatively. Magnetic resonance imaging was performed to assess postoperative tendon healing and thickness at the original tear site.At 1-year follow-up, clinical scores improved significantly (P .0001) and the mean tendon thickness increased by 2.0 mm (P .0001). Magnetic resonance imaging evidence of complete healing was found in 8 patients and a considerable reduction in defect size was shown in 23, whereas 1 lesion remained stable. In 1 noncompliant patient with a high-grade articular lesion, progression to a full-thickness tear occurred while shoveling snow 1 month after surgery. No serious adverse events related to the implant were reported.Arthroscopic implantation of a bioinductive collagen scaffold is a safe and effective treatment for intermediate- to high-grade partial-thickness rotator cuff tears of the supraspinatus tendon.

Postsurgical pain, like that associated with major upper extremity surgery, can be significant and usually require the use of opioid analgesics. However, opioids are associated with significant adverse effects, including respiratory depression, which often drive the use of multimodal therapy with nonopioid analgesics, including local and regional analgesia techniques. However, use of older local anesthetics provides a limited duration of analgesia. An innovative formulation of liposomal bupivacaine (Exparel), which is approved for surgical site infiltration, can provide a longer duration of analgesia. Because optimal pain relief relies on the success of the surgical site infiltration technique, a group convened to address best practices for periarticular injection techniques for shoulder surgery. This article reviews the neuroanatomy of the shoulder, recommends optimal solutions (i.e., analgesic cocktails) and volume for injection, and provides a detailed description of the infiltration technique to develop the best approach to periarticular injection for major shoulder surgery.

The promise of precision medicine will only be fully realized if the research community can adapt its clinical trials methodology to study molecularly characterized tumors instead of the traditional histologic classification. Such trials will depend on adequate tissue collection, availability of quality controlled, high throughput molecular assays, and the ability to screen large numbers of tumors to find those with the desired molecular alterations. The National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is well positioned to conduct such trials. The NCTN has the ability to seamlessly perform ethics review, register patients, manage data, and deliver investigational drugs across its many sites including both in cities and rural communities, academic centers, and private practices. The initial set of trials will focus on different questions: (1) Exceptional Responders Initiative—why do a minority of patients with solid tumors or lymphoma respond very well to some drugs even if the majority do not?; (2) NCI MATCH trial—can molecular markers predict response to targeted therapies in patients with advanced cancer resistant to standard treatment?; (3) ALCHEMIST trial—will targeted epidermal growth factor receptor ( EGFR) and anaplastic lymphoma kinase ( ALK) inhibitors improve survival for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer Master Protocol trial for advanced squamous cell lung cancer—is there an advantage to developing drugs for small subsets of molecularly characterized tumors in a single, multiarm trial design? These studies will hopefully spawn a new era of treatment trials that will carefully select the tumors that may respond best to investigational therapy.

Posterior subluxation is commonly seen in overhead and collision athletes. It can result from a traumatic event disrupting the posterior labrum or repetitive movements that create a posterior capsular pouch. The retroversion of the humerus and glenoid, combined with the natural internal rotation of the arm at rest, can create additional symptoms with routine daily activity. Symptomatic posterior instability in patients that does not respond to conservative management can be repaired with a high degree of successful stabilization using arthroscopic techniques. Labral repair with suture anchors, combined with posteroinferior capsular plication, has returned many athletes to their prior sport. Additional findings, including reverse humeral capsular avulsions, can be repaired at the same time.

Background The recurrence score (RS) based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low. There is little information from prospective clinical trials, however, regarding outcomes for patients with a high RS treated with chemotherapy regimens including taxanes and/or anthracyclines. Methods Women with hormone-receptor-positive, HER2-negative, axillary-node-negative breast cancer and a high RS of 26-100 were assigned to receive endocrine therapy plus a chemotherapy regimen selected by the treating physician. Results Among the 9719 eligible women, 1389 (14%) had a RS of 26-100.The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-FU in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). The estimated rates of freedom from recurrence of breast cancer at a distant site were 93.0% (standard error [SE]+0.8%) at 5 years and 86.8% (SE + 1.7%) at 9 years. In contrast, the projected rates of freedom from distant recurrence in this population if treated with endocrine therapy alone was estimated to be 78.8% (SE ± 14.0%) at 5 years and 65.4% (SE ± 10.4%) at 9 years when estimating outcomes based on the treatment effect of chemotherapy noted in the HER2-negative cohort of the B20 trial. Five-year rates of freedom from distant recurrence ranged from 92.3% to 95.5% for all chemotherapy regimens with the exception of CMF (88.5%). Conclusions The estimated rate of freedom from distant recurrence in women with a RS of 26-100 treated with a variety of adjuvant taxane and/or anthracycline-containing chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population. Clinical trial identification NCT00310180. Legal entity responsible for the study ECOG-ACRIN Cancer Research Group. Funding USA National Cancer Institute, Genomic Health. Disclosure All authors have declared no conflicts of interest.

Surgical repair of the unstable shoulder begins with reattachment of the detached capsulolabral complex. The degree of damage to the glenohumeral articulation can be variable and is often related to the degree of trauma, duration of dislocation, and the number of instability events. There have been many surgical procedures proposed for the treatment of shoulder instability in the athlete, ranging from soft-tissue repair to coracoid transfer or the addition of a bone graft. The arthroscope provides an opportunity to visualize and repair the injured structures, returning the shoulder to maximal range of motion and permitting functional improvement. Indications for arthroscopic anterior stabilization include a first-time dislocation, patients with apprehension following dislocation, and recurrent dislocation and subluxation prior to creating advanced bone loss. If there is advanced bone loss, an augmented repair or a procedure other than arthroscopic stabilization has been recommended. Mobilization of the anterior capsule and fixation to recreate the proper anterior tension will limit translation and potential recurrence of instability. The steps of the arthroscopic anterior stabilization include: 1. Perform examination under anesthesia to identify the directions and degree of humeral translation relative to the glenoid. 2. Position the patient with the shoulder 30° abducted and 20° flexed. 3. Create proper portals, including a posterior viewing portal, dual anterior portals, and accessory portals for suture anchor placement. 4. Perform a diagnostic arthroscopy to determine the damaged structures and how they relate to shoulder positions that may invite future dislocations. 5. Perform capsule and labrum mobilization to permit anatomic relocation of the injured ligament. 6. Place a series of suture anchors along the anterior and inferior glenoid margin. 7. Utilize suture hooks to retrieve the sutures placed through the capsule to advance the capsule superiorly to the glenoid margin. 8. Assess glenoid deficiency and place an autograft anterior to the damaged glenoid rim in selected cases. 9. Tenodese the posterior capsule and infraspinatus to a large Hill-Sachs lesion on the posterosuperior aspect of the humeral head in selected cases. 10. Repair additional labral structures superiorly and posteriorly if they contribute to glenohumeral instability. The anticipated outcome is a return to sport and high-demand activities. Bracing is available, but the internal repair is the most reliable technique to protect the glenohumeral articulation. Additional techniques can be implemented when added trauma has resulted in severe bone loss of the glenoid, humeral head, or anterior capsular structures. A return to high-risk activities can be anticipated in 4 to 7 months.

The massive rotator cuff tear is a challenging problem for the shoulder surgeon [1–3]. Large and massive tears include multiple rotator cuff tendons with varying degrees of retraction [4]. Treatment of multitendon tears may result in a residual defect following arthroscopic or open repair [5–7].

As part of the White House Cancer Moonshot Initiative, the National Cancer Institute (NCI) has developed a drug formulary to provide investigational anticancer agents to the extramural research community. This article describes how the NCI Formulary functions, how researchers may apply for access to drugs in the formulary, and the NCI's initial goals for formulary participation. Approved investigators may apply for access to formulary agents at: https://nciformulary.cancer.gov.

Arthroscopic shoulder stabilization offers several potential advantages compared with open surgery, including the opportunity to more accurately evaluate the glenohumeral joint at the time of diagnostic assessment; comprehensively address multiple pathologic lesions that may be identified; and avoid potential complications unique to open stabilization, such as postoperative subscapularis failure. A thorough understanding of normal shoulder anatomy and biomechanics, along with the pathoanatomy responsible for anterior, posterior, and multidirectional shoulder instability patterns, is very important in the management of patients who have shoulder instability. The treating physician also must be familiar with diagnostic imaging and physical examination maneuvers that are required to accurately diagnose shoulder instability.

We review how overall survival (OS) comparisons should be interpreted with increasing availability of effective therapies that can be given subsequently to the treatment assigned in a randomized clinical trial (RCT). We examine in detail how effective subsequent therapies influence OS comparisons under varying conditions in RCTs. A subsequent therapy given after tumor progression (or relapse) in an RCT that works better in the standard arm than the experimental arm will lead to a smaller OS difference (possibly no difference) than one would see if the subsequent therapy was not available. Subsequent treatments that are equally effective in the treatment arms would not be expected to affect the absolute OS benefit of the experimental treatment but will make the relative improvement in OS smaller. In trials in which control arm patients cross over to the experimental treatment after their condition worsens, a smaller OS difference could be observed than one would see without cross-overs. In particular, use of cross-over designs in the first definitive evaluation of a new agent in a given disease compromises the ability to assess clinical benefit. In disease settings in which there is not an intermediate end point that directly measures clinical benefit, OS should be the primary end point of an RCT. The observed difference in OS should be considered the measure of clinical benefit to the patients, regardless of subsequent therapies, provided that the subsequent therapies used in both treatment arms follow the current standard of care.

The goal of this study was to estimate prevalence of HER-2 positive tumors in a population-based sample of 1026 women diagnosed in 2005 with early stage breast cancer. We modeled the relationship between patient and tumor characteristics and HER-2. HER-2 positive estimates were 19% for women aged ≤49 years and 15% aged ≥50 years. HER-2 varied by tumor grade and size in women aged ≤49 years but was not significant in multivariate analysis. Tumor grade and race were associated with HER-2 for women aged ≥50 years after controlling for other variables. HER-2 varies by age and by race and tumor in older women.

Presented are recommendations of the Data Submission Standards and Evidence Requirements panel from the Conference on Clinical Cancer Research along with the U.S. Food and Drug Administration's response to these recommendations.

Purpose In 2001, the National Cancer Institute (NCI) formed the Central Institutional Review Board (CIRB) to conduct a single human subjects review for its multisite phase III oncology trials. The goal of this study was to assess whether NCI's CIRB was associated with lower effort, time, and cost in processing adult phase III oncology trials. Methods We conducted an observational study and compared sites affiliated with the NCI CIRB to unaffiliated sites that used their local IRB for review. Oncology research staff and IRB staff were surveyed to understand effort and timing. Response rates were 60% and 42%, respectively. Analysis of these survey data yielded information on effort, timing, and costs. We combined these data with CIRB operational data to determine the net savings of the CIRB using a societal perspective. Results CIRB affiliation was associated with faster reviews (33.9 calendar days faster on average), and 6.1 fewer hours of research staff effort. CIRB affiliation was associated with a savings of $717 per initial review. The estimated cost of running the CIRB was $161,000 per month. The CIRB yielded a net cost of approximately $55,000 per month from a societal perspective. Whether the CIRB results in higher or lower quality reviews was not assessed because there is no standard definition of review quality. Conclusion The CIRB was associated with decreases in investigator and IRB staff effort and faster protocol reviews, although savings would be higher if institutions used the CIRB as intended.

MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole.An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out.In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033).Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408–16. ©2016 AACR. See related commentary by Mileham and Kim, p. 5397

Postsurgical pain, like that associated with major upper extremity surgery, can be significant and usually require the use of opioid analgesics. However, opioids are associated with significant adverse effects, including respiratory depression, which often drive the use of multimodal therapy with nonopioid analgesics, including local and regional analgesia techniques. However, use of older local anesthetics provides a limited duration of analgesia. An innovative formulation of liposomal bupivacaine (Exparel), which is approved for surgical site infiltration, can provide a longer duration of analgesia. Because optimal pain relief relies on the success of the surgical site infiltration technique, a group convened to address best practices for periarticular injection techniques for shoulder surgery. This article reviews the neuroanatomy of the shoulder, recommends optimal solutions (i.e., analgesic cocktails) and volume for injection, and provides a detailed description of the infiltration technique to develop the best approach to periarticular injection for major shoulder surgery.