The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six ...clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.
This case report shows a unique case of Castleman's disease in the context of histopathological diagnosis of cutaneous melanoma where clinical and radiological features of Castleman's disease were ...masked by presumptive diagnosis of metastatic melanoma. The disease is part of a group of lymphoproliferative disorders with characteristic histopathological features that can occur in any lymph node in the body, characterised by slow growing painless masses which are asymptomatic until mass effect occurs. This case highlights the need for caution when considering management of lymphadenopathy with clinically/radiologically suspicious nodes.
A 65 year old man with metastatic melanoma of the left elbow presented for axillary sentinel node mapping and was found to have a hypoechoic enlarged node on ultrasound. This was further investigated and found to be a lymphoproliferative growth pathognomonic for Castlemans disease.
Whilst clinically detected lymphadenopathy in the draining node basin of a primary cutaneous melanoma is highly suspicious for nodal metastasis, it is sometimes not possible to confirm or exclude this diagnosis without complete histological examination of the node. Multidisciplinary input from the surgeon, histopathologist and radiologist is a key step in confirming diagnosis.
Alternative diagnoses must be considered in the context of lymphadenopathy, even in the context of malignant melanoma.
•Castleman’s disease is a key differential to consider in the context of lymphadenopathy•Even in the context of melanoma, lymphadenopathy is not always attributable to metastatic disease•Radiological diagnosis of lymphadenopathy can give clues to aid differentials but histopathological examination is the gold standard for diagnosis
Aims
Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation ...interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.
Design, Setting and Participants
We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on‐line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review.
Measurements
Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery.
Findings
Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty‐titration, bias modification, goal‐setting, strategy learning and meta‐awareness as active ingredients; and (iv) both addiction treatment work‐force and specialized neuropsychologists facilitating delivery, together with novel digital‐based delivery modalities.
Conclusions
Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher‐order cognitive skills via well‐validated intervention approaches qualified with mechanistic techniques and flexible delivery options.
Preoperative patient optimization is increasingly recognized as key to good surgical outcomes. Preoperative hyponatremia is a modifiable risk factor linked to poorer postoperative outcomes in other ...surgical fields. We provide the first investigation of the association of preoperative hyponatremia with morbidity and mortality in patients undergoing cervical spine surgery.
We queried the National Surgical Quality Improvement Program registry for patients who underwent cervical spine fusion. Preoperative serum sodium levels were classified as normal (135–145 mEq/L) or hyponatremic (<135 mEq/L); hypernatremic patients were excluded from the analysis. Multivariable logistic analyses using a multiple imputations methodology were performed to determine significant predictors of major morbidity and mortality (MMM).
We included 20,817 patients, of whom 5.2% were hyponatremic at presentation. Preoperative hyponatremia was a significant predictor of MMM (odds ratio OR, 1.23; 95% confidence interval CI, 1.09–1.39), mortality (OR, 1.36; 95% CI, 1.03–1.77), major morbidity (OR, 1.24; 95% CI, 1.10–1.40), and odds of prolonged hospitalization (OR, 1.13; 95% CI, 1.04–1.23). Other significant predictors of MMM included age, undergoing an emergent versus nonemergent operation, having chronic obstructive pulmonary disease, having disseminated malignancy, being functionally dependent, presenting with sepsis or septic shock, and having an American Society of Anesthesiologists status of 3, 4, or 5. Similar results were seen in analyses using only complete cases and in sensitivity analyses.
Using the National Surgical Quality Improvement Program database, hyponatremia is observed in approximately 1 in every 20 patients undergoing cervical spine fusion. More importantly, it is a predictor of mortality, major morbidity, and prolonged hospitalization. From a systems-level perspective, preoperative hyponatremia may therefore represent a point of intervention for preoperative patient optimization.
Background
Predicting which patients with American Joint Committee on Cancer (AJCC) T1–T2 melanomas will have a positive sentinel lymph node (SLN) is challenging. Melanoma Institute Australia (MIA) ...developed an internationally validated SLN metastatic risk calculator. This study evaluated the nomogram’s impact on T1–T2 melanoma patient management at MIA.
Methods
SLN biopsy (SLNB) rates were compared for the pre- and post-nomogram periods of 1 July 2018–30 June 2019 and 1 August 2020–31 July 2021, respectively.
Results
Overall, 850 patients were identified (pre-nomogram, 383; post-nomogram, 467). SLNB was performed in 29.0% of patients in the pre-nomogram group and 34.5% in the post-nomogram group (
p
= 0.091). The overall positivity rate was 16.2% in the pre-nomogram group and 14.9% in the post-nomogram group (
p
= 0.223). SLNB was performed less frequently in T1a melanoma patients in the pre-nomogram group (1.1%,
n
= 2/177) than in the post-nomogram group (8.6%,
n
= 17/198)
p
≤ 0.001. This increase was particularly for melanomas with a risk score ≥ 5%, with an SLN positivity rate of 11.8% in the post-nomogram group (
p
= 0.004) compared with zero. For T1b melanomas with a risk score of > 10%, the SLNB rate was 40.0% (8/20) pre-nomogram and 75.0% (12/16) post-nomogram (
p
= 0.049).
Conclusions
In this specialized center, the SLN risk calculator appears to influence practice for melanomas previously considered low risk for metastasis, with increased use of SLNB for T1a and higher-risk T1b melanomas. Further evaluation is required across broader practice settings. Melanoma management guidelines could be updated to incorporate the availability of nomograms to better select patients for SLNB than previous criteria.
More than 120,000 anterior cervical discectomy and fusions (ACDFs) are performed annually. Pseudarthrosis is a potential delayed adverse event that affects up to 33% of patients. The degree to which ...this adverse event affects both patient quality-of-life (QOL) outcomes and health care costs is poorly understood.
Patients who underwent revision surgery for pseudarthrosis between 2007 and 2012 were identified and matched to controls not experiencing pseudarthrosis in a 1:2 fashion (case/control). Cases and controls were compared regarding total health care costs incurred in the year after the index ACDF and QOL outcomes on the following metrics: EuroQol Five-Dimensions Questionnaire, Patient Health Questionnaire–9, and Pain Disability Questionnaire.
Of 738 patients who underwent ACDF, 11 underwent surgery for pseudarthrosis. No differences were noted between cases and controls regarding any of the matched variables. Patients in the pseudarthrosis cohort had poorer postoperative scores on the EuroQol Five-Dimensions Questionnaire mobility, usual activities, pain/discomfort, and quality-adjusted life-year dimensions. In addition, 64% of patients with pseudarthrosis had worsened quality-adjusted life-year scores compared with only 9% of controls (P < 0.01). Patients with pseudarthrosis also had poorer mental health (P < 0.01) and pain disability outcomes (P < 0.01) than did controls. Pseudarthrosis was associated with significant increases in direct costs, direct postoperative costs, and total costs (all P < 0.01).
This is the first study to characterize the effect of surgical revision for pseudarthrosis on both QOL outcomes and care costs after ACDF. Patients requiring revision experienced significantly poorer QOL outcomes and higher care costs relative to controls.
Improvements in recurrence-free survival (RFS) were demonstrated in two recent randomized trials for patients with sentinel node (SN)-negative stage IIB or IIC melanoma receiving adjuvant systemic ...therapy (pembrolizumab/nivolumab). However, adverse events also occurred. Accurate individualized prognostic estimates of RFS and overall survival (OS) would allow patients to more accurately weigh the risks and benefits of adjuvant therapy. Since the current American Joint Committee on Cancer eighth edition (AJCC-8) melanoma staging system focuses on melanoma-specific survival, we developed a multivariable risk prediction calculator that provides estimates of 5- and 10-year RFS and OS for these patients.
Data were extracted from the Melanoma Institute Australia (MIA) database for patients diagnosed with stage II (clinical or pathological) melanoma (n = 3,220). Survival prediction models were developed using multivariable Cox regression analyses (MIA models) and externally validated twice using data sets from the United States and the Netherlands. Each model's performance was assessed using C-statistics and calibration plots and compared with Cox models on the basis of AJCC-8 staging (stage models).
The 5-year and 10-year RFS C-statistics were 0.70 and 0.73 (MIA-model) versus 0.61 and 0.60 (stage-model), respectively. For OS, the 5-year and 10-year C-statistics were 0.71 and 0.75 (MIA-model) compared with 0.62 and 0.61 (stage-model), respectively. The MIA models were well calibrated and externally validated.
The MIA models offer accurate and personalized estimates of both RFS and OS in patients with stage II melanoma even in the absence of pathological staging with SN biopsy. These models were robust on external validations and may be used in everyday practice both with (ideally) and without performing SN biopsy to identify high-risk patients for further management strategies. An online tool will be available at the MIA website (Risk Prediction Tools).
Background
Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to ...determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes.
Methods
Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database.
Results
The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of postoperative complications did not differ between the NAST- and upfront surgery-treated patients (55% vs. 51%;
p
= 0.643), and steroid treatment for drug toxicity did not influence the complication rate (odds ratio OR, 1.1; 95% confidence interval CI, 0.4–3;
p
= 0.826). No significant differences in postoperative morbidity were observed in terms of seroma (23% vs. 11%;
p
= 0.570) or lymphedema (36% vs. 51%;
p
= 0.550). The rate of achieving a textbook outcome was comparable for the two groups (61% vs. 57%;
p
= 0.641).
Conclusions
The surgical outcomes after lymph node dissections were comparable between the patients who received NAST and those who had upfront surgery, indicating that surgery can be safely performed after NAST with TT or ICI for stage III melanoma.
