Two-year outcomes with a bioinductive collagen implant used in augmentation of arthroscopic repair of full-thickness rotator cuff tears: final results of a prospective multicenter study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 by >90% 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. CONCLUSION: 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.

Isolated bioinductive repair of partial-thickness rotator cuff tears using a resorbable bovine collagen implant: two-year radiologic and clinical outcomes from a prospective multicenter study.

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.

Surgical treatment for recurrent shoulder instability: factors influencing surgeon decision making.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Editorial Commentary: Improving Strength and Clinical Outcomes After Rotator Cuff Repair-Role of Choosing Single- Versus Double-Row Repair.

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.

Editorial Commentary: We Need to Customize Surgical Treatment When Treating Patients With Recurrent Anterior Shoulder Instability.

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.

Radiologic and clinical evaluation of a bioabsorbable collagen implant to treat partial-thickness tears: a prospective multicenter study.

BACKGROUND: 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. 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. 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. RESULTS: 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. CONCLUSIONS: 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.

Arthroscopic Management of Anterior, Posterior, and Multidirectional Shoulder Instabilities.

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.

Best Practices for Periarticular Infiltration With Liposomal Bupivacaine for the Management of Pain After Shoulder Surgery: Consensus Recommendation.

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.

Preoperative planning with three-dimensional CT vs. three-dimensional magnetic resonance imaging does not change surgical management for shoulder instability.

Background: This study aims to determine the effect of time and imaging modality (three-dimensional (3D) CT vs. 3D magnetic resonance imaging (MRI)) on the surgical procedure indicated for shoulder instability. The hypothesis is there will be no clinical difference in procedure selection between time and imaging modality. Methods: Eleven shoulder surgeons were surveyed with the same ten shoulder instability clinical scenarios at three time points. All time points included history of present illness, musculoskeletal exam, radiographs, and standard two-dimensional MRI. To assess the effect of imaging modality, survey 1 included 3D MRI while survey 2 included a two-dimensional and 3D CT scan. To assess the effect of time, a retest was performed with survey 3 which was identical to survey 2. The outcome measured was whether surgeons made a "major" or "minor" surgical change between surveys. Results: The average major change rate was 14.1% (standard deviation: 7.6%). The average minor change rate was 12.6% (standard deviation: 7.5%). Between survey 1 to the survey 2, the major change rate was 15.2%, compared to 13.1% when going from the second to the third survey (P = .68). The minior change rate between the first and second surveys was 12.1% and between the second to third interview was 13.1% (P = .8). Discussion: The findings suggest that the major factor related to procedural changes was time between reviewing patient information. Furthermore, this study demonstrates that there remains significant intrasurgeon variability in selecting surgical procedures for shoulder instability. Lastly, the findings in this study suggest that 3D MRI is clinically equivalent to 3D CT in guiding shoulder instability surgical management. Conclusion: This study demonstrates that there is significant variability in surgical procedure selection driven by time alone in shoulder instability. Surgical decision making with 3D MRI was similar to 3D CT scans and may be used by surgeons for preoperative planning.

An audit strategy for time-to-event outcomes measured with error: application to five randomized controlled trials in oncology.

BACKGROUND: Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern. Blinded-independent central review (BICR) of all images from a trial is commonly undertaken to mitigate differential measurement-error bias that may be present in hazard ratios (HRs) based on local evaluations. Similar BICR and local evaluation HRs may provide reassurance about the treatment effect, but BICR adds considerable time and expense to trials. METHODS: We describe a BICR audit strategy [2] and apply it to five randomized controlled trials to evaluate its use and to provide practical guidelines. The strategy requires BICR on a subset of study subjects, rather than a complete-case BICR, and makes use of an auxiliary-variable estimator. RESULTS: When the effect size is relatively large, the method provides a substantial reduction in the size of the BICRs. In a trial with 722 participants and a HR of 0.48, an average audit of 28% of the data was needed and always confirmed the treatment effect as assessed by local evaluations. More moderate effect sizes and/or smaller trial sizes required larger proportions of audited images, ranging from 57% to 100% for HRs ranging from 0.55 to 0.77 and sample sizes between 209 and 737. LIMITATIONS: The method is developed for a simple random sample of study subjects. In studies with low event rates, more efficient estimation may result from sampling individuals with events at a higher rate. CONCLUSION: The proposed strategy can greatly decrease the costs and time associated with BICR, by reducing the number of images undergoing review. The savings will depend on the underlying treatment effect and trial size, with larger treatment effects and larger trials requiring smaller proportions of audited data.

Arthroscopic repair techniques for massive rotator cuff tears.

Patients with massive rotator cuff tears present with pain, weakness, and loss of function. Candidates for arthroscopic repair include symptomatic, young, active patients; those with an acute tear or tears with early changes of atrophy; and patients willing to comply with recovery and rehabilitation processes after surgery. As massive rotator cuff tears extend, the glenohumeral articulation is destabilized, allowing superior migration. Repair of the force couples and reinforcement of the anterosuperior rotator cuff cable can restore functional elevation via the deltoid. Muscle changes, including rotator cuff atrophy and fatty infiltration, will affect shoulder strength and function. As chronic changes become more extensive (such as the absence of the acromiohumeral interval and degenerative joint changes), other repair options may be more durable. Other arthroscopic options, including partial rotator cuff closure, graft to augment the repair, and use of the long head of the biceps tendon, have been helpful in pain relief and functional gains.

Actionable Tumor Alterations and Treatment Protocol Enrollment of Pediatric and Young Adult Patients With Refractory Cancers in the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.

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.

Retear rates and clinical outcomes at 1 year after repair of full-thickness rotator cuff tears augmented with a bioinductive collagen implant: a prospective multicenter study.

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 <65 years of age had significantly better CMS scores at 1 year when compared with those with retear and those ≥65 years (P < .05). There was no statistically significant difference in outcomes based on treatment of the biceps tendon. Of 9 reported reoperations in the operative shoulder, only 2 were considered potentially related to the collagen implant. CONCLUSION: Interim results from this prospective study indicate a favorable rate of retear relative to the literature and improvement in clinical function at 1 year after adjunctive treatment with the study implant augmenting standard arthroscopic repair techniques.

Network for Biomarker Immunoprofiling for Cancer Immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC).

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.

Population-based estimate of the prevalence of HER-2 positive breast cancer tumors for early stage patients in the US.

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.

NIH and NCI support for development of novel therapeutics in gynecologic cancer: a user's guide.

The development of novel therapeutics is a lengthy and often tortuous process. It frequently spans the identification of new targets, preclinical validation, discovery and refinement of novel therapies, safety studies, phase O, 1, 2, and 3 trials, and reverse translation. NIH and NCI provide via web sites a variety of resources and research tools of great value to investigators. NCI also provides tissue resources useful for discovery and validation, as well as extensive support for preclinical drug development. The NCI's effective partnership with industry and academia, as well as the ongoing NCI-supported clinical trials network, facilitates clinical development of novel therapeutics. Specialized NCI programs focused on cancer imaging, radiation research, and complementary and alternative medicine, also assist the development of novel agents. Finally, the NIH and the NCI sponsor a variety of grant mechanisms, supporting institutions, consortia, and individuals, which investigators seeking to develop novel therapeutics should make themselves familiar.

Arthroscopic management of shoulder instabilities: anterior, posterior, and multidirectional.

Arthroscopy is considered a relatively new technique for the surgical repair of an unstable shoulder. Shoulder arthroscopy has grown in popularity and is considered the gold standard for treating carefully selected patients. Despite its increasing popularity, the procedure has a significant learning curve and has resulted in early higher recurrence rates when compared with patients treated with open techniques. With the addition of newer instrumentation, the refinement of techniques, and additional capsular plication and tensioning, outcomes for patients treated with shoulder arthroscopy should continue to improve. A major distinguishing feature in selecting appropriate candidates for shoulder arthroscopy is whether there have been significant bone changes resulting from dislocation recurrence. Recurrent anterior dislocation may create an anterior glenoid rim fracture, erosion loss from multiple recurrences, and an impression defect on the posterior aspect of the humeral head. The loss of contact area between the "ball and cup" may compromise the results of techniques that restore the anatomic restraints of soft tissues. Early intervention is becoming recognized as an important factor in patient selection for arthroscopic treatment. Imaging studies after traumatic injuries include radiographs, CT scans, possible articular contrast studies, and MRIs. These studies can identify and quantify rim fractures and the remaining articular contact in patients with recurrent subluxations, allowing for earlier appropriate intervention. Patients with significant bone loss may be best treated with an open procedure that allows grafting of the deficiency. Arthroscopic techniques to repair fractures or graft deficiencies continue to evolve. Rim fractures can be anatomically repaired with a suture anchor technique when recognized early. Rim erosion from chronic recurrent dislocations may require a combination of soft-tissue reattachment and coracoid grafting. Humeral head defects may require either soft-tissue or bone grafting to avoid engagement with the anterior edge of the glenoid. These techniques require arthroscopic skill and experience and are currently being performed as open procedures. In the future, it is likely that arthroscopy will be involved in the entire spectrum of treatment for shoulder instability.

Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH).

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.