Baseline circulating tumour DNA and total metabolic tumour volume as early outcome predictors in aggressive large B-cell lymphoma. A real-world 112-patient cohort.

Approximately 20%-50% of patients with large B-cell lymphoma (LBCL) experience poor outcomes. We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single-centre study included 112 newly diagnosed LBCL patients, receiving R-CHOP/R-CHOP-like chemotherapies. CtDNA load was calculated following next-generation sequencing of cell-free DNA (cfDNA) using a targeted 40-gene lymphopanel. TMTV was measured using a fully automated artificial intelligence-based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3.15 log haploid genome equivalents per mL. TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3.57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1-year PFS (44% vs. 83%, p < 0.001 and 64% vs. 97%, p = 0.002, respectively). When combined, three prognostic groups were identified. The shortest PFS was observed when both TMTV and ctDNA load were high (p < 0.001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high-risk patients could benefit from CAR T-cell therapy or bispecific antibodies as first-line treatments.

[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Optimization of whole-body 2-[18F]FDG-PET/MRI imaging protocol for the initial staging of patients with myeloma.

OBJECTIVE: To determine the optimal 2-[18F]FDG-PET/MRI imaging protocol for the initial staging of patients with suspected or confirmed multiple myeloma. METHODS: Radiologists and nuclear medicine specialists reviewed all PET/MRI exams of 104 patients with a monoclonal gammopathy (MG). The presence of focal and diffuse bone marrow involvement (BMI) was assessed using 4 different image datasets: WB-MRI, PET, WB-PET/MRI, and WB-DCE-PET/MRI. A reference standard was established by a panel review of all baseline and follow-up imaging, and biological and pathological information. The diagnostic performance for each image dataset to detect BMI was evaluated and compared (Fisher's exact test). RESULTS: Sensitivity, specificity, and accuracy for focal BMI of WB-MRI was 87%, 97%, and 92%; of PET was 78%, 97%, and 95%; of WB-PET/MRI was 93%, 97%, and 95%; and of WB-DCE-PET/MRI was 93%, 97%, and 95%, respectively. WB-PET/MRI and WB-DCE-PET/MRI were statistically superior to PET (p = 0.036) without decreasing specificity. The sensitivity, specificity, and accuracy of WB-MRI for diffuse BMI detection was 91%, 80%, and 85%; of 3DT1-PET was 53%, 89%, and 74%; of WB-PET/MRI was 98%, 66%, and 79%; and of WB-DCE-PET/MRI was 98%, 59%, and 75%, respectively. PET lacked sensitivity compared to all other dataset studies (p < 0.0001). WB-MRI had the best accuracy without reaching statistical significance when compared to the other datasets. CONCLUSION: The WB-PET/MRI dataset including T1 and T2 Dixon, WB-DWI, and PET images provides optimal diagnostic performance to detect both focal lesions and diffuse BMI, with limited added value of WB-DCE for baseline staging of patients with MG. Key Points • The combination of morphological and functional MRI sequences and metabolic (2-[18F]FDG-PET) images increases the diagnostic performance of PET/MRI to detect focal bone lesions. • The adjunction of dynamic contrast-enhanced sequences did not improve diagnostic performance.

Fully automatic segmentation of diffuse large B cell lymphoma lesions on 3D FDG-PET/CT for total metabolic tumour volume prediction using a convolutional neural network.

PURPOSE: Lymphoma lesion detection and segmentation on whole-body FDG-PET/CT are a challenging task because of the diversity of involved nodes, organs or physiological uptakes. We sought to investigate the performances of a three-dimensional (3D) convolutional neural network (CNN) to automatically segment total metabolic tumour volume (TMTV) in large datasets of patients with diffuse large B cell lymphoma (DLBCL). METHODS: The dataset contained pre-therapy FDG-PET/CT from 733 DLBCL patients of 2 prospective LYmphoma Study Association (LYSA) trials. The first cohort (n = 639) was used for training using a 5-fold cross validation scheme. The second cohort (n = 94) was used for external validation of TMTV predictions. Ground truth masks were manually obtained after a 41% SUVmax adaptive thresholding of lymphoma lesions. A 3D U-net architecture with 2 input channels for PET and CT was trained on patches randomly sampled within PET/CTs with a summed cross entropy and Dice similarity coefficient (DSC) loss. Segmentation performance was assessed by the DSC and Jaccard coefficients. Finally, TMTV predictions were validated on the second independent cohort. RESULTS: Mean DSC and Jaccard coefficients (± standard deviation) in the validations set were 0.73 ± 0.20 and 0.68 ± 0.21, respectively. An underestimation of mean TMTV by - 12 mL (2.8%) ± 263 was found in the validation sets of the first cohort (P = 0.27). In the second cohort, an underestimation of mean TMTV by - 116 mL (20.8%) ± 425 was statistically significant (P = 0.01). CONCLUSION: Our CNN is a promising tool for automatic detection and segmentation of lymphoma lesions, despite slight underestimation of TMTV. The fully automatic and open-source features of this CNN will allow to increase both dissemination in routine practice and reproducibility of TMTV assessment in lymphoma patients.

Extracardiac soft tissue uptake, evidenced on early 99mTc-HMDP SPECT/CT, helps typing cardiac amyloidosis and demonstrates high prognostic value.

PURPOSE: Increased cardiac uptake (CU) on early-phase 99mTc-HMDP scintigraphy has demonstrated diagnostic and prognostic values in amyloid transthyretin (ATTR) cardiac amyloidosis (CA). Extracardiac uptake (ECU) has been poorly studied. We assessed the clinical value of ECU, in combination with CU, on 99mTc-HMDP scintigraphy using a novel Methodological Amyloidosis Diagnostic Index (MADI). METHODS: We reviewed all patients referred for suspicion of CA, who underwent 99mTc-HMDP scintigraphy over an 8-year period. ECU, CU, and MADI were determined: MADI0 = neither ECU or CU, MADI1 = ECU alone, MADI2 = CU alone, and MADI3 = ECU + CU. RESULTS: Of 308 eligible patients, 247 had CA, including 75 ATTRv, 107 ATTRwt, and 65 light-chain (AL), while 61 had another cardiopathy (controls). ECU was observed in 29% of CA and 3% of controls. Most frequent sites of ECU were pleuropulmonary (16% of CA, 3% of controls) followed by the digestive tract and subcutaneous tissues. The liver and spleen ECU was only observed in AL-CA (n = 8). CU was only observed in CA patients (n = 187), of whom 182 had ATTR-CA vs. 5 AL-CA, P < 0.001. MADI0 was only observed in controls (97%) and in AL-CA (60%). MADI1 was mainly observed in AL-CA (positive predictive value, PPV = 91%) while MADI2/3 were more frequent in ATTR-CA (PPV = 97%), P < 0.0001. MADI > 0 vs. MADI0 in AL and MADI3 vs. MADI2 in ATTR were associated with a worse prognosis (P = 0.03 and P = 0.002, respectively). CONCLUSIONS: ECU combined with CU demonstrates high diagnostic and prognostic values in CA patients. MADI seems an easy and reliable score in clinical practice.

Prognostic value of anthropometric measures extracted from whole-body CT using deep learning in patients with non-small-cell lung cancer.

INTRODUCTION: The aim of the study was to extract anthropometric measures from CT by deep learning and to evaluate their prognostic value in patients with non-small-cell lung cancer (NSCLC). METHODS: A convolutional neural network was trained to perform automatic segmentation of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscular body mass (MBM) from low-dose CT images in 189 patients with NSCLC who underwent pretherapy PET/CT. After a fivefold cross-validation in a subset of 35 patients, anthropometric measures extracted by deep learning were normalized to the body surface area (BSA) to control the various patient morphologies. VAT/SAT ratio and clinical parameters were included in a Cox proportional-hazards model for progression-free survival (PFS) and overall survival (OS). RESULTS: Inference time for a whole volume was about 3 s. Mean Dice similarity coefficients in the validation set were 0.95, 0.93, and 0.91 for SAT, VAT, and MBM, respectively. For PFS prediction, T-stage, N-stage, chemotherapy, radiation therapy, and VAT/SAT ratio were associated with disease progression on univariate analysis. On multivariate analysis, only N-stage (HR = 1.7 [1.2-2.4]; p = 0.006), radiation therapy (HR = 2.4 [1.0-5.4]; p = 0.04), and VAT/SAT ratio (HR = 10.0 [2.7-37.9]; p < 0.001) remained significant prognosticators. For OS, male gender, smoking status, N-stage, a lower SAT/BSA ratio, and a higher VAT/SAT ratio were associated with mortality on univariate analysis. On multivariate analysis, male gender (HR = 2.8 [1.2-6.7]; p = 0.02), N-stage (HR = 2.1 [1.5-2.9]; p < 0.001), and the VAT/SAT ratio (HR = 7.9 [1.7-37.1]; p < 0.001) remained significant prognosticators. CONCLUSION: The BSA-normalized VAT/SAT ratio is an independent predictor of both PFS and OS in NSCLC patients. KEY POINTS: • Deep learning will make CT-derived anthropometric measures clinically usable as they are currently too time-consuming to calculate in routine practice. • Whole-body CT-derived anthropometrics in non-small-cell lung cancer are associated with progression-free survival and overall survival. • A priori medical knowledge can be implemented in the neural network loss function calculation.

Long-term complications and reconstruction failures in previously radiated breast cancer patients receiving salvage mastectomy with autologous reconstruction or tissue expander/implant-based reconstruction.

Salvage mastectomy (SM) is the standard of care for patients with local recurrence (LR) after breast conservation therapy (BCT), often with immediate reconstruction. Complications of reconstruction are a concern for these patients, and long-term data are limited. We sought to compare rates of complications requiring re-operation (CRR) and reconstruction failure (RF) between autologous reconstruction (AR) and tissue expander/implant reconstruction (TE/I). Patients with locally recurrent breast cancer after BCT, treated with SM and immediate AR or TE/I between 2000 and 2008, were identified. CRR was defined as unplanned return to operating room for wound infection, dehiscence, necrosis (including flap, skin, or fat), hematoma, or hernia (for AR) and extrusion, leak, or capsular contracture (for TE/I). RF was defined as conversion to another reconstruction technique or to flat chest wall. This study included 103 patients with 107 reconstructions. Median follow-up was 6.6 years. CRR and RF were significantly higher with TE/I (n = 34) compared to AR (n = 73) at 5 years (50.9% vs 25.5%; P = 0.02) and (42.1% vs 5.8%; P < 0.001). On univariate analysis (UVA), TE/I (HR = 2.14; P = 0.02) and diabetes (HR = 5.10; P = 0.007) were significant predictors for CRR. On UVA, TE/I (HR = 7.30; P < 0.001) and older age at reconstruction (HR = 1.03; P = 0.003) were significant predictors for RF. In this population of previously irradiated patients, TE/I was associated with significantly higher CRR and RF. Complications continue to occur up to 10 years after TE/I. AR should be considered in appropriately selected patients, though TE/I may remain a reasonable option in patients without high-risk factors for surgical complications.

Challenges in Microsurgical Reconstruction for Craniofacial Osteomyelitis With Resultant Osteonecrosis.

INTRODUCTION: Chronic osteomyelitis is characterized by compromised blood supply and eventual osteonecrosis. Definitive treatment requires aggressive resection of affected bone. The resultant defect poses a unique challenge to reconstructive surgeons. Much of the literature on craniofacial osteomyelitis focuses on infection eradication, rather than subsequent reconstruction. This article reports representative cases from our experience with free flap reconstruction for defects secondary to chronic osteomyelitis of the craniofacial skeleton. METHODS/RESULTS: The authors selected 5 of the most difficult reconstructive cases of craniofacial osteomyelitis from our experience in a single tertiary referral institution with a follow-up of at least 6 months. Three of the 5 cases arose in the setting of previous head and neck cancer treated with resection and radiation therapy. One case had a previous surgical craniotomy complicated by osteomyelitis and multiple failed alloplastic reconstructions. The final case was due to multiple gunshots to the head, with subsequent cerebral and cranial abscess (>1000cc). In each case, the defect was successfully treated with free tissue transfer. Two cases required creation of recipient vessels with an arteriovenous loop. CONCLUSIONS: Free tissue transfer provides a versatile and effective tool in the reconstruction of extensive craniofacial osteomyelitis defects. Furthermore, the addition of vascularized tissue can protect against further episodes of osteomyelitis. Finally, arteriovenous loops can be employed successfully when prior radiation and infection of the wound bed precludes the use of local recipient target vessels.

Apical sparing pattern of left ventricular myocardial 99mTc-HMDP uptake in patients with transthyretin cardiac amyloidosis.

BACKGROUND: A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA). OBJECTIVES: Aim was to investigate the left ventricular (LV) regional distribution of early-phase 99mTc-Hydroxymethylene diphosphonate (99mTc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA). METHODS: All patients underwent a whole-body planar 99mTc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical). RESULTS: Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial 99mTc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of 99mTc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10-6). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%]; P < 10-6), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10-7) and remained constant independently of the TTR mutation subtype with P ranging 10-5 to 0.03. CONCLUSIONS: Early-phase myocardial scintigraphy identified regional distribution of 99mTc-HMDP uptake characterized by a base-to-apex gradient, corroborating echocardiographic, and cardiac magnetic resonance findings. This apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.

Determining the False-Negative Rate Using Fluorescence Image-Assisted Sentinel Lymph Node Biopsy in Cutaneous Melanoma.

INTRODUCTION: Despite the advances in cutaneous melanoma management, the false-negative rates (FNRs) of sentinel lymph node biopsy (SLNB) are still high. These rates are dependent not only on the technique but also on definitional terms and percentage of head/neck melanoma (highest false-negative SLNB). Fluorescence imaging technology is well acquainted in plastic surgery and other specialties. Having demonstrated that fluorescence-assisted SLNB is effective in melanoma, we are interested in determining its FNR. METHODS: We obtained institutional review board approval to follow up prospectively all patients with cutaneous melanoma who underwent radioisotope/fluorescence-assisted SLNB with the intent to capture 100 negative SLNB patients. Inclusion criteria were as follows: (1) National Comprehensive Cancer Network criteria; (2) an SLNB report; (3) at least 24 months of follow-up in the negative SLNB group. The outcome variables were FNR and adjusted FNR of SLNB, considering the criterion standard of assessing the accuracy of SNLB. The FNR was defined as the proportion of patients with false-negative SLNB to patients with true-positive and false-negative SLNB [false negative/(false negative + true positive)]. Adjusted FNR refers to the previously described false-negative SLNB, but in the absence of local/in-transit recurrence or distant metastases. Furthermore, false-negative incidence (false-negative/negative SLNB patients) was also calculated. Length of follow-up was date of surgery to the date of last follow-up/death. RESULTS: A total of 125 participants, with 52.0% being male and 48.0% being female, were included. One hundred patients had an SLNB negative for metastases, whereas the rest had positive SLNB results. Median follow-up time of the cohort and that of the negative SLNB group were 36.7 (2.6-58.5) and 37.9 (24.0-58.5) months, respectively. A relatively high number (24.8%) of head/neck melanoma were included. We identified 2 cases of false-negative SLNB, with one having in-transit metastases. Thus, the FNR and adjusted FNR were 7.4% and 3.7%, respectively. The false-negative incidence and adjusted false-negative incidence were 2.0% and 1.0%, respectively. CONCLUSIONS: This is the first prospective study examining the FNR of fluorescence-assisted SLNB for patients with cutaneous melanoma. Our study reveals that this technique has one of the lowest FNRs published, especially considering the large percentage of participants with head/neck melanoma involved.

Maximizing the Reach of the Pedicled Gastrocnemius Muscle Flap: A Comparison of 2 Surgical Approaches.

BACKGROUND: The medial gastrocnemius muscle flap is commonly used for the reconstruction of defects around the knee and proximal leg. The flap can be raised using either a medial or a posterior midline incision, although no studies have been done comparing the 2 different surgical approaches. METHODS: We compared the reach of the medial gastrocnemius muscle flap using either of the 2 incisions in a series of 25 fresh cadavers. All muscle flaps were elevated without division of the muscle origin. Muscle reach was calculated using the distance from a fixed bony point with the leg fully extended and the muscle under no tension. Muscle width measurements were used to calculate surface area of coverage. RESULTS: Muscle flaps elevated through the posterior midline incision group reached 2.02 cm farther than flaps through the medial incision (P < 0.05). This resulted in 20.3 cm increase in surface area for the posterior midline incision group over the medial incision group (P < 0.05). The posterior midline incision allowed for better visualization of the vascular pedicle and dissection of fascial attachments around the pes anserinus. CONCLUSIONS: The posterior midline incision for the elevation of the medial gastrocnemius pedicled muscle flap allows for a safe, thorough mobilization of the muscle resulting in increased muscle reach and increased surface area when compared with the medial incision. Furthermore, the posterior midline incision provides better access to the gastrocnemius muscle origin and the lateral muscle head.

Traumatic Facial Myopericytoma: A Differential to Consider.

Myopericytoma is a slow-growing, benign soft tissue neoplasm that arises from perivascular smooth muscle cells. This tumor is a rare entity itself, but it is only scarcely mentioned in the literature occurring secondary to trauma. The authors report a 21-year-old male patient who presented with a pulsatile mass in the medial canthal area where he had experienced previous trauma from a car accident 1-year prior. The mass was excised and histopathology revealed myopericytoma. This clinical report adds to the limited body of evidence supporting trauma as an etiology for this rare tumor.

The Anterolateral Thigh Flap as the Flap of Choice for Scalp Reconstruction.

INTRODUCTION: Large scalp soft tissue defects can present difficulties with reconstruction. The ideal flap for scalp reconstruction has yet to be described although the latissimus dorsi flap is frequently referred to as the first choice in this setting. PATIENTS AND METHODS: Following institutional review board approval, the authors reviewed their experience in scalp reconstruction for the past 4 years. Patient demographics, reconstruction indication, flap choice, complications, and outcomes were recorded. RESULTS: Thirteen patients underwent scalp reconstruction with an anterolateral thigh (ALT) free flap. In most patients, the indication was resection of a cutaneous malignancy. In all but 1 patient the facial or more proximal vessels were used for anastomosis. None of the patients required vein grafts to increase pedicle length. The median flap surface area was 156 cm. One flap had vascular compromise. All donor sites healed without complications. DISCUSSION: The ALT flap can emerge as the flap of choice for scalp reconstruction, even when proximal neck vessels are used as the recipient targets. Using a suprafascial dissection and extending the vascular pedicle to the profunda femoris artery can optimize its role in this setting. The ALT flap provides excellent cosmesis and durable scalp coverage with minimal donor site morbidity.

Age as a Risk Factor in Abdominoplasty.

Background: Recent studies reviewing large patient databases suggested that age may be an independent risk factor for abdominoplasty. However, these investigations by design considered only short-term major complications. Objectives: The purpose of this investigation was: (1) to compare the safety of abdominoplasty in an elderly and younger patient population; (2) to determine the complication rates across all spectrums: major, minor, local, and systemic; and (3) to evaluate complications occurring both short and long term. Methods: Abdominoplasty procedures performed from 2010 to 2015 were retrospectively reviewed. Subjects were divided into two groups: ≤59 years old and ≥60 years old. Major, minor, local, and systemic complications were analyzed. Patient demographics, comorbidities, perioperative details, adjunctive procedures were also assessed. Results: A total of 129 patients were included in the study: 43 in the older and 86 in the younger age group. The median age of The elderly and young groups was 65.0 and 41.5 years, respectively (P < .001). No statistically significant differences in major, minor, local, or systemic complications were found when both age groups were compared. Major local, major systemic, minor local, and minor systemic in the elderly were 6.9%, 2.3%, 18.6%, and 2.3%, while in the younger patients were 9.3%, 4.7%, 10.5%, and 0.0%, respectively (P > .05). Median follow-up time of the elderly (4.0 months) was no different than the younger (5.0 months) patients (P > .07). Median procedure time in the elderly (4.5 hours) was no different than the younger group (5.0 hours) (P = .4). The elderly exhibited a greater American Society of Anesthesiologist score, median body mass index (28.7 vs 25.1 kg/m2), and number of comorbidities (2.7 vs 0.9) (P < .001). Conclusions: There was no significant difference in either major or minor complications between the two groups. This suggests that with proper patient selection, abdominoplasty can be safely performed in the older age patient population. Level of Evidence: 2.

Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

Complications Following Abdominal-Based Free Flap Breast Reconstruction: Is a 30 days Complication Rate Representative?

PURPOSE: The purpose of this study was to analyze timing and frequency of complications following free tissue autologous reconstruction in a single tertiary care institution. METHODS: From August 2012 to December 2013, all patients operated on for abdominal-based free flap breast reconstruction at a single institution were included. Complications were identified and risk factors associated with them were analyzed using SPSS software. RESULTS: The total number of patients was 130 with a total of 191 flaps (69 for unilateral and 61 for bilateral reconstructions). Mean surgery time was 570.5 min (±151.24). Fifty-nine of the reconstructed breasts (30.8 %) had early complications. Reoperations due to complications were required in 16 (8.3 %) of the breasts during the first 30 days with seven patients requiring multiple reoperations. Twenty-eight patients required reoperations after 30 days, the most frequent reason being delayed wound healing and abdominal hernia. The most significant complication was a case of disseminated infection with loss of skin coverage of the breasts. Early complications and donor-site complications were higher in active smokers (p = 0.005 and p < 0.001, respectively). Patients with a BMI < 25 had fewer total early complications (p = 0.05), as well as fewer complications on the breast area (p = 0.02). A longer time in the operating room was associated with an increase in late complications (p = 0.018). Bilateral/unilateral operation, immediate/delayed surgery, radiotherapy, age, hypertension, diabetes, and surgery time were not associated with early complications, late complications, or reoperations (p > 0.05). CONCLUSIONS: Active smoking was found to be a significant risk factor for early complications, reoperations, and donor-site complications. Patients with a normal BMI had fewer early complications, reoperations at 30 days, and complications on the breast area. As a significant number of complications occurred beyond the standard 30-day reporting period, it is important to consider reoperations during an extended period. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prognostic Value of 18F-FDG PET Radiomics Features at Baseline in PET-Guided Consolidation Strategy in Diffuse Large B-Cell Lymphoma: A Machine-Learning Analysis from the GAINED Study.

The results of the GA in Newly Diagnosed Diffuse Large B-Cell Lymphoma (GAINED) study demonstrated the success of an 18F-FDG PET-driven approach to allow early identification-for intensification therapy-of diffuse large B-cell lymphoma patients with a high risk of relapse. Besides, some works have reported the prognostic value of baseline PET radiomics features (RFs). This work investigated the added value of such biomarkers on survival of patients involved in the GAINED protocol. Methods: Conventional PET features and RFs were computed from 18F-FDG PET at baseline and extracted using different volume definitions (patient level, largest lesion, and hottest lesion). Clinical features and the consolidation treatment information were also considered in the model. Two machine-learning pipelines were trained with 80% of patients and tested on the remaining 20%. The training was repeated 100 times to highlight the test set variability. For the 2-y progression-free survival (PFS) outcome, the pipeline included a data augmentation and an elastic net logistic regression model. Results for different feature groups were compared using the mean area under the curve (AUC). For the survival outcome, the pipeline included a Cox univariate model to select the features. Then, the model included a split between high- and low-risk patients using the median of a regression score based on the coefficients of a penalized Cox multivariate approach. The log-rank test P values over the 100 loops were compared with a Wilcoxon signed-ranked test. Results: In total, 545 patients were included for the 2-y PFS classification and 561 for survival analysis. Clinical features alone, consolidation features alone, conventional PET features, and RFs extracted at patient level achieved an AUC of, respectively, 0.65 ± 0.07, 0.64 ± 0.06, 0.60 ± 0.07, and 0.62 ± 0.07 (0.62 ± 0.07 for the largest lesion and 0.54 ± 0.07 for the hottest). Combining clinical features with the consolidation features led to the best AUC (0.72 ± 0.06). Adding conventional PET features or RFs did not improve the results. For survival, the log-rank P values of the model involving clinical and consolidation features together were significantly smaller than all combined-feature groups (P < 0.007). Conclusion: The results showed that a concatenation of multimodal features coupled with a simple machine-learning model does not seem to improve the results in terms of 2-y PFS classification and PFS prediction for patient treated according to the GAINED protocol.

Fat embolism after liposuction in Klippel-Trenaunay syndrome.

Fat embolism syndrome (FES) is a rare but potentially fatal postoperative complication from liposuction. We present the case of a 24-year-old woman with Klippel-Trenaunay syndrome who developed FES as a complication of lower extremity liposuction. There may be an increased risk of FES in patients with vascular malformations undergoing liposuction.

Is There a Role of Artificial Intelligence in Preclinical Imaging?

This review provides an overview of the current opportunities for integrating artificial intelligence methods into the field of preclinical imaging research in nuclear medicine. The growing demand for imaging agents and therapeutics that are adapted to specific tumor phenotypes can be excellently served by the evolving multiple capabilities of molecular imaging and theranostics. However, the increasing demand for rapid development of novel, specific radioligands with minimal side effects that excel in diagnostic imaging and achieve significant therapeutic effects requires a challenging preclinical pipeline: from target identification through chemical, physical, and biological development to the conduct of clinical trials, coupled with dosimetry and various pre, interim, and post-treatment staging images to create a translational feedback loop for evaluating the efficacy of diagnostic or therapeutic ligands. In virtually all areas of this pipeline, the use of artificial intelligence and in particular deep-learning systems such as neural networks could not only address the above-mentioned challenges, but also provide insights that would not have been possible without their use. In the future, we expect that not only the clinical aspects of nuclear medicine will be supported by artificial intelligence, but that there will also be a general shift toward artificial intelligence-assisted in silico research that will address the increasingly complex nature of identifying targets for cancer patients and developing radioligands.

Validation of the ΔSUVmax for Interim PET Interpretation in Diffuse Large B-Cell Lymphoma on the Basis of the GAINED Clinical Trial.

The GAINED phase 3 trial (ClinicalTrials.gov identifier: NCT01659099) evaluated a PET-driven consolidative strategy in patients with diffuse large B-cell lymphoma. In this post hoc analysis, we aimed to compare the prognostic value of the per-protocol PET interpretation criteria (Menton 2011 consensus) with the change in the SUVmax (ΔSUVmax) alone. Methods: Real-time central review of 18F-FDG PET/CT was performed in 581 patients after 2 cycles (PET2) and 4 cycles (PET4) of immunochemotherapy using the Menton 2011 criteria, combining the ΔSUVmax (cutoffs of 66% and 70% at PET2 and PET4, respectively) and the Deauville scale. In "special cases," when the baseline SUVmax was less than 10.0 or the interim residual tumor SUVmax was greater than 5.0, the Menton 2011 experts' consensus agreed that the ΔSUVmax may not be reliable and that the Deauville score is preferable. Prognostic values of Menton 2011 and ΔSUVmax were evaluated by Kaplan-Meier analyses in terms of progression-free survival (PFS). Results: Seventeen percent of patients at PET2 (100/581) and 8% at PET4 (49/581) had PET-negative results by ΔSUVmax but were considered to have PET-positive results according to Menton 2011 with residual SUVmax of greater than 5.0. For the population with PET2-positive results, 2-y PFS was 70% (range, 58%-80%) with ΔSUVmax alone, whereas the outcome tended to be better for those who were considered to have PET-positive results by Menton 2011, 81% (range, 72%-87%). Conversely, all 10 patients with baseline SUVmax of less than 10.0 had PET2-positive results by ΔSUVmax but were considered to have PET2-negative results by Menton 2011. These patients had the same 2-y PFS as patients with PET2-negative/PET4-negative results, indicating that the ΔSUVmax yielded false-positive results in this situation. Conclusion: We recommend the use of the ΔSUVmax alone rather than the Menton 2011 criteria for assessing the interim metabolic response in patients with diffuse large B-cell lymphoma, except when the baseline SUVmax is less than 10.0.