Response to commentary on "Cumulative rib fracture risk after stereotactic body radiotherapy in patients with localized non-small cell lung cancer" by Tugcu et al.

Kirkelund Bentsen K ，Brink C ，Bjørn Nielsen T ，Bank Lynggaard R ，Just Vinholt P ，Schytte T ，Hansen O ，Starup Jeppesen S ... -  《-》

Far Posterior Approach for Rib Fracture Fixation: Surgical Technique and Tips.

The present video article describes the far posterior or paraspinal approach to posterior rib fractures. This approach is utilized to optimize visualization intraoperatively in cases of far-posterior rib fractures. This technique is also muscle-sparing, and muscle-sparing posterolateral, axillary, and anterior approaches have been shown to return up to 95% of periscapular strength by 6 months postoperatively1. Like most fractures, the skin incision depends on the fracture position. The vertical incision is made either just medial to a line equidistant between the palpable spinous processes and medial scapular border or directly centered over the fracture line in this region. The incision and superficial dissection must be extended cranially and caudally, approximately 1 or 2 rib levels past the planned levels of instrumentation, in order to allow muscle elevation and soft-tissue retraction. Superficial dissection reveals the trapezius muscle, with its fibers coursing from inferomedial to superolateral caudal to the scapular spine, and generally coursing transversely above this level. The trapezius is split in line with its fibers (or elevated proximally at the caudal-most surface), and the underlying layer will depend on the location of the incision. The rhomboid minor muscle overlies ribs 1 and 2, the rhomboid major muscle overlies ribs 3 to 7, and the latissimus dorsi overlies the remaining rib levels. To avoid muscle transection, the underlying muscle is also split in line with its fibers. Next, the thoracolumbar fascia is encountered and sharply incised, revealing the erector spinae muscles, which comprise the spinalis thoracis, longissimus thoracis, and iliocostalis thoracis muscles. These muscles and their tendons must be sharply elevated from lateral to midline; electrocautery is useful for this because there is a robust blood supply in this region. Medially, while retracting the paraspinal musculature, visualization with this approach can extend to the head and neck of the rib, and even to the spine. Following deep dissection, the fractures are now visualized. During fracture reduction, it is critical to assess reduction of both the costovertebral joint and the costotransverse joint. With fractures closer to the spine, it is recommended to have at least 2 cm between the rib head and tubercle in order to allow 2 plate holes to be positioned on the neck of the rib; if comminution exists and plating onto the transverse process is needed, several screws are required here for stability as well. For appropriate stability if plating onto the spine is not required, a minimum of 3 locking screws on each side of the fracture are recommended. Contouring of the plates to match the curvature of the rib and to allow for proper apposition may be required with posterior rib fractures. Screws must be placed perpendicular to the rib surface. Following operative stabilization of the rib fractures, a layered closure is performed, and a soft dressing is applied. Nonoperative alternatives include non-opioid and opioid medications as well as corticosteroid injections for pain control. Supportive mechanical ventilation and physiotherapy breathing exercises can also be implemented as needed. Operative alternatives include open reduction and internal fixation utilizing conventional locking plates and screws. Rib fractures are often treated nonoperatively when nondisplaced because of the surrounding soft-tissue support2,3. According to Chest Wall Injury Society guidelines, contraindications to surgical fixation of rib fractures include patients requiring ongoing resuscitation; rib fractures involving ribs 1, 2, 11, or 12, which are relative contraindications; severe traumatic brain injury; and acute myocardial infarction. Patient age of <18 years is also a relative contraindication for the operative treatment of rib fractures. The current literature does not recommend surgical fixation in this age group because these fractures typically heal as the patient ages; however, fracture-dislocations may require the use of instrumentation to prevent displacement. Currently, the U.S. Food and Drug Administration does not approve most plating systems for patients <18 years old4. In certain cases, including those with substantial displacement, persistent respiratory distress, pain, or fracture nonunion, stabilization with open reduction and internal fixation may be appropriate5-7. In cases of flail chest injuries, surgery is often indicated6. Flail chest injuries have been noted in the literature to have an incidence of approximately 150 cases per 100,000 injuries and have been shown to carry a mortality rate of up to 33%8,9. Surgical treatment of rib fractures has been shown to be associated with a decreased hospital length of stay and mortality rate in patients with major trauma1. Expected outcomes of this procedure include low complication rates, decreased hospital and intensive care unit length of stay, and reduced mechanical ventilation time10,11. However, as with any procedure, there are also risks involved, including iatrogenic lung injury from long screws or an aortic or inferior vena cava injury with aggressive manipulation of displaced fractured fragments, especially on the left side of the body. During open reduction, there is also a risk of injuring the neurovascular bundle. Tanaka et al. demonstrated a significant reduction in the rate of postoperative pneumonia in their operative group (22%) compared with their nonoperative group (90%)12. Schuette et al. demonstrated a 23% rate of postoperative pneumonia, 0% mortality at 1 year, an average of 6.2 days in the intensive care unit, an average total hospital length of stay of 17.3 days, and an average total ventilator time of 4 days in the operative group10. Prins et al. reported a significantly lower incidence of pneumonia in operative (24%) versus nonoperative patients (47.3%; p = 0.033), as well as a significantly lower 30-day mortality rate (0% versus 17.7%; p = 0.018)3. This procedure utilizes a muscle-sparing technique, which has demonstrated successful results in the literature on the use of the posterolateral, axillary, and anterior approaches, returning up to 95% of periscapular strength, compared with the uninjured shoulder, by 6 months postoperatively1. The use of a muscle-sparing technique with the far-posterior approach represents a topic that requires further study in order to compare the results with the successful results previously shown with other approaches. The ipsilateral extremity can be prepared into the field to allow its intraoperative manipulation in order to achieve scapulothoracic motion and improved subscapular access.For costovertebral fracture-dislocations, the vertical incision line is made just medial to a line equidistant between the palpable spinous processes and medial scapular border.Lateral decubitus positioning can be utilized to allow for simultaneous access to fractures that extend more laterally and warrant a posterolateral approach; however, it is generally more difficult to access the fracture sites near the spine with this approach.This muscle-sparing technique is recommended to optimize postoperative periscapular strength, as previously demonstrated with other approaches.Incision and superficial dissection must be extended cranially and caudally approximately 1 or 2 rib levels past the planned levels of instrumentation in order to allow muscle elevation and soft-tissue retraction.To avoid muscle transection during surgical dissection, the underlying muscle is split in line with its fibers.During deep dissection, it can be difficult to delineate underlying muscles because these muscles have fibers that do not run in line with the trapezius, and some, like the rhomboid major, run nearly perpendicular to it.Electrocautery is useful while elevating the erector spinae muscles and tendons, as there is a robust blood supply in this region.The erector spinae muscle complex is relatively tight and adherent to the underlying ribs, which may make it difficult to achieve adequate visualization; therefore, at least 3 rib levels must be elevated to access a rib for reduction and instrumentation.Although internal rotation deformities are more common in this region, any external displacement of a fracture can lead to a muscle injury that can be utilized for access.During fracture reduction, it is critical to assess reduction of both the costovertebral joint and the costotransverse joint.Special attention must be given to contouring the implants because there are not any commercially available precontoured implants for this region at this time, and plating onto the spine remains an off-label use of any currently available implant.For the more challenging fracture patterns, the use of a right-angled power drill and screwdriver is recommended.Generally, the incision is utilized as previously described to provide access as far medial as the transverse process if needed. However, in cases in which this approach does not allow proper visualization with rib fracture-dislocations involving the posterior ribs or spine, a midline spinal incision can be utilized while working in combination with a spine surgeon.With fractures closer to the spine, it is recommended to have at least 2 cm between the rib head and tubercle in order to allow 2 plate holes to be positioned on the neck of the rib.If comminution exists and plating onto the transverse process is needed, several screws are required for stability.When measuring the length of screws to be placed in the transverse process, preoperative CT scans can be utilized. CT = computed tomographyCWIS = Chest Wall Injury SocietyIVC = inferior vena cava.

Manes TJ ，DeGenova DT ，Taylor BC ，Patel JN ... -  《-》

Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial.

Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC. In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA. Patients were eligible if they had stage II-III, unresectable, locally advanced NSCLC (any histology), with peripheral or central primary tumours that were 7 cm or smaller, excluding central tumours within 2 cm of involved nodal disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients who had previously received systemic therapy or radiotherapy were excluded. Participants received SBRT to the primary tumour (50-54 Gy in three to five fractions) followed by standard radiotherapy (planned up to 60 Gy in 30 2 Gy fractions) to the involved lymph nodes with concurrent platinum doublet chemotherapy (either paclitaxel 50 mg/m2 intravenously plus carboplatin area under the curve 2 mg/mL per min every 7 days for a total of six 1-week cycles or etoposide 50 mg/m2 intravenously on days 1-5 and days 29-33 plus cisplatin 50 mg/m2 intravenously on days 1, 8, 29, and 36 for two cycles of 4 weeks). An amendment to the protocol (Dec 11, 2017) permitted the administration of consolidation durvalumab at the discretion of the treating investigator. An additional protocol amendment on Jan 13, 2021, directed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab (10 mg/kg intravenously on day 1 and day 15 of a 4-week cycle for up to 12 cycles or 1500 mg intravenously on day 1 of a 4-week cycle for up to 12 cycles). The primary endpoint was 1-year progression-free survival (per Response Evaluation Criteria in Solid Tumours version 1.1), assessed in all participants who received at least one fraction of SBRT and had radiological follow-up data up to 1 year. A 1-year progression-free survival rate of greater than 60% was required to reject the null hypothesis and show significant improvement in 1-year progression-free survival. One-sided exact binomial tests were used to compare the primary endpoint versus the historical control 1-year progression-free survival rate used to determine the sample size. Safety was assessed in all patients who received at least one fraction of SBRT. This study is registered with ClinicalTrials.gov, NCT03141359, and is closed to accrual. Between May 11, 2017, and June 27, 2022, 61 patients were enrolled and received at least one dose of fractionated SBRT, of whom 59 were evaluable for the primary endpoint. Median age was 67 years (IQR 61-72), 28 (46%) of 61 were female, 33 (54%) were male, 51 (84%) were White, seven (11%) were Black, and three (5%) were of other or unknown race. Of the 61 patients enrolled, 47 received at least one dose of consolidation durvalumab. As of data cutoff (July 12, 2023), median follow-up was 29·5 months (IQR 14·9-47·1). 1-year progression-free survival was 62·7% (90% CI 51·2-73·2; one-sided p=0·39, compared with the historical control rate), with 37 of 59 evaluable participants progression free and alive 1 year after enrolment (n=14 progressed, n=8 died). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (nine [15%] of 61 patients), decreased white blood cell count (five [8%]), and anaemia (four [7%]). Treatment-related serious adverse events occurred in 11 (18%) of 61 patients, which included lung infection (three [5%]), pneumonitis (two [3%]), decreased neutrophil count (two [3%]), febrile neutropenia (two [3%]), and dyspnoea, hypoxia, respiratory failure, sinus tachycardia, bronchial infection, and acute kidney injury (each in one [2%] patient). Treatment-related deaths occurred in four (7%) of 61 patients (one each of respiratory failure, respiratory failure and dyspnoea, lung infection, and pneumonitis). Although this study did not meet the primary endpoint, activity and safety profiles of primary lung tumour SBRT followed by concurrent mediastinal chemoradiotherapy were favourable compared with other modern trials treating locally advanced NSCLC with chemoradiotherapy. These findings serve as the basis for the ongoing randomised phase 3 study NRG Oncology LU008 (NCT05624996). AstraZeneca and Atrium Health Levine Cancer Institute.

Heinzerling JH ，Mileham KF ，Robinson MM ，Symanowski JT ，Induru RR ，Brouse GM ，Corso CD ，Prabhu RS ，Haggstrom DE ，Moeller BJ ，Bobo WE ，Fasola CE ，Thakkar VV ，Pal SE ，Gregory JM ，Norek SL ，Begic XJ ，Kesarwala AH ，Burri SH ，Simone CB 2nd ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

First Report of Twig Dieback Caused by Neopestalotiopsis rosae on Highbush Blueberry in the Continental United States.

Dietsch B ，Yuan X ，Goslin J ，Harbach CJ ，Slack SM ... -  《-》