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Purpose: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. Methods: We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate ( n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of Tc-MAA and Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BED) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. Results: MAA and Y biodistributions were not different (71 % of cases), different in 23 % and uncertain in 6 %. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted ( p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50 %) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14 %, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD ≈ 75 Gy. Conclusion: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [Y]DOTA-TATE and [Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (Y) and a medium-energy beta/gamma emitter (Lu) in patients with metastatic NET refractory to conventional therapy. Methods: A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [Lu]DOTA-TATE (5.55 GBq) and [Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Results: Administration of tandem [Y]DOTA-TATE and [Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment Conclusion: The results of our study indicates that combined [Y]DOTA-TATE and [Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. [ABSTRACT FROM AUTHOR]

The aim of this study was to carry out two different dose estimation approaches in patients with non-Hodgkin’s lymphoma (NHL) treated with a myeloablative amount of 90Y-labelled ibritumomab tiuxetan (Zevalin®) in an open-label dose escalation study. Twenty-seven patients with relapsed/refractory or de novo high-risk NHL receiving one myeloablative dose of 90Y-ibritumomab tiuxetan followed by tandem stem cell reinfusion were evaluated for dose estimate. The injected activity was 30 MBq/kg in 12 patients and 45 MBq/kg in 15 patients. Dose estimation was performed 1 week prior to 90Y-ibritumomab tiuxetan by injection of 111In-ibritumomab tiuxetan (median activity: 200 MBq). The absorbed dose (D) and the biologically effective dose (BED) were calculated. The absorbed doses per unit activity (Gy/GBq) were [median (range)]: heart wall 4.6 (2.5–9.7), kidneys 5.1 (2.8–10.5), liver 6.1 (3.9–10.4), lungs 2.9 (1.5–6.8), red marrow 1.0 (0.5–1.7), spleen 7.0 (1.5–14.4) and testes 4.9 (2.9–16.7). The absorbed dose (Gy) for the 15 patients treated with 45 MBq/kg were: heart wall 17.0 (8.7–25.4), kidneys 17.1 (7.9–22.4), liver 20.8 (15.4–28.3), lungs 8.1 (5.4–11.4), red marrow 3.1 (2.0–4.0), spleen 26.2 (17.0–35.6) and testes 17.3 (9.0–28.4). At the highest activities the acute haematological toxicity was mild or moderate and of very short duration, and it was independent of the red marrow absorbed dose. No secondary malignancy or treatment-related myelodysplastic syndrome was observed. No non-haematological toxicity (liver, kidney, lung) was observed during a follow-up period of 24–48 months. The use of 45 MBq/kg of 90Y-ibritumomab tiuxetan in association with stem cell autografting resulted in patients being free of toxicity in non-haematological organs. These clinical findings were in complete agreement with our dose estimations, considering both organ doses and BED values. [ABSTRACT FROM AUTHOR]

Introduction: CS is characterized by flushing, diarrhea and carcinoid heart disease (CHD) alone or in association. Aim(s): To assess the incidence, clinical features and survival of WDNETs pts with CS. Materials and methods: We retrospectively analyzed 700 NET pts, between 1979 to 2009. One-hundred and ten pts with Typical (T) or Atypical (A) CS were identified. Results: Incidence of CS was 15.7%, with a prevalence of 7.5/700 cases. Median age was 55.5 years, male/female = 59/51. All pts were WDNETs and 83% were GEP: Carcinoids/pNET= 66%/34%; Midgut/Foregut/ Hindgut= 44%/35.5%/3.3%. Liver involvement was found in 96%: synchronous (42%); metacronous (68%). Primary tumor resection was performed in 67% of midgut and in 33% of foregut. TCS was evident in 92/110 (83.3%), whilst ACS in 2/110 (2.2%). The most common symptoms were flushing/diarrhea/CHD in 72 %/64%/12 % of pts. CgA/NSE/HIAA levels were pathologic in 78%/22%/50%, respectively, mOS was 90 months (range 2-274), 5- and 10-year survival rates were 58% and 43% respectively. Significant difference in mOS was found between male/female 114/90 months; midgut/foregut 114/74 months; carcinoids/pNET 131/74 months (p<0.05). Primary tumor resection may be correlated with survival amelioration. Conclusion: The advanced stage and, in particular, the liver involvement could be the main factor related to the CS appearance. The status of functional or nonfunctional NET could be mostly correlated to tumor load involvement rather than to primary tumor site, which still remains the main prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: This paper outlines the consensus of the Italian Association for Neuroendocrine Tumors(Itanet), the Italian Association of Nuclear Medicine (AIMN), the Italian Society of Endocrinology (SIE), and the Italian Association of Medical Oncology (AIOM) on treating neuroendocrine neoplasms (NENs)with radioligand therapy (RLT)., Methods: A list of 10 questions regarding using RLT ingastroenteropancreatic neuroendocrine tumors (GEP-NETs) was addressed after a careful review of theavailable literature. compiling information from the MEDLINE database, augmented with expert opinionsand recommendations, aligns with the latest scientific research and the author's extensive knowledge.The recommendations are evaluated using the GRADE system, showcasing the level of evidence andthe strength of the recommendations., Results and Conclusions: Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines., Competing Interests: Declarations. Conflict of interest: MA received honoraria as consultants from AAA, Novartis and Recordati outside the submitted work, CMG received honoraria as consultants from Novartis and ITM outside the submitted work, MC received honoraria as consultants from AAA, Novartis, Advanz, Harpoon Therapeutics, Merck, Harbour Biomedical outside the submitted work, AF received honoraria as support for research project and scientific organization from Novartis and Ipsen, NF received honoraria as consultants and speakers from Novartis and ITM outside the submitted work, FS received honoraria as consultants and speakers from AAA, outside the submitted work, MM received honoraria as consultants and speakers from AAA, outside the submitted work. The other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this manuscript., (© 2024. The Author(s).)

Purpose: Pre-treatment [ 99m Tc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [ 99m Tc]TcMAA-based segmentation of tumor and normal tissue compartments., Materials and Methods: Included patients had HCC treated by glass [ 90 Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [ 99m Tc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [ 99m Tc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [ 99m Tc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient., Results: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [ 99m Tc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [ 99m Tc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [ 99m Tc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80)., Conclusion: Real-world data support [ 99m Tc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [ 90 Y]yttrium microspheres. Both anatomic and [ 99m Tc]TcMAA threshold methods were suitable for treatment planning., Trial Registration Number: NCT03295006., Competing Interests: Declarations. Conflicts of Interest/Competing interests: Marnix Lam, MD, PhD: Is a consultant for Boston Scientific, Terumo and Quirem Medical. He receives research support from Boston Scientific, Terumo and Quirem Medical. The UMC Utrecht receives royalties from Quirem Medical. Etienne Garin, MD, PhD: Serves as a consultant for Boston Scientific. Paul Haste, MD: Is a consultant for Boston Scientific. Alban Denys, MD, MSc: Is a consultant for Cook, Neuwave, and received grants from Johnson and Johnson. Brian Geller, MD: Nothing to disclose. S. Cheenu Kappadath, PhD: Is a consultant for Boston Scientific, Sirtex Medical, and Terumo Medical. He receives research support from Boston Scientific, Sirtex Medical and ABK Biomedical. Cuneyt Turkmen, MD: Is a consultant for Boston Scientific. Daniel Y Sze, MD, PhD: Was a consultant for Argon, Artio Medical, Astra-Zeneca, Bayer, BlackSwan Vascular, Boston Scientific, Bristol Meyers Squibb, Eisai, FludX, W.L. Gore, Guerbet, Koli, Sirtex, Terumo, TriSalus, and Varian; received institutional research support from Boston Scientific, W.L. Gore, Merit Medical, and Sirtex; held equity in BlackSwan Vascular, Confluent Medical, Koli, Proteus Digital Health, Radiaction, and TriSalus; and serves on data safety monitoring boards for W.L. Gore and Replimune. Hamad Saleh Alsuhaibani, MD: Nothing to disclose. Ken Herrmann, MD: Reports personal fees from Bayer, personal fees and other from Sofie Bioscienes, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from Boston Scientific, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work. Marco Maccauro, MD: Nothing to disclose. Murat Cantasdemir, MD: Is a consultant for Boston Scientific. Matthew Dreher, PhD: Works for Boston Scientific. Kirk D. Fowers, PhD: Works for Boston Scientific. Vanessa Gates, PhD: Is a consultant for Boston Scientific. Riad Salem, MD: Is a consultant for Boston Scientific, AstraZeneca, Genentech, Sirtex, Cook, Eisai, Bard and QED Therapeutics. Ethics approval: Not Applicable. Consent to participate: Not Applicable., (© 2024. The Author(s).)

Purpose: In Peptide Receptor Radionuclide Therapy (PRRT) with [ 177 Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [ 177 Lu]Lu-DOTATATE therapeutic regimen., Methods: The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD&#95;TOT was calculated as the mean between cycle 1 (GTD&#95;1) and 4 (GTD&#95;4) multiplied by 4. Patients were followed-up for median 32.8 (range 18-45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months., Results: The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD&#95;1 and GTD&#95;TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD&#95;1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 - 37]). Using GTD&#95;TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD&#95;1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD&#95;1., Discussion: Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of 177 Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m)., Conclusion: Tumour dosimetry after the first administration of [ 177 Lu]Lu-DOTATATE offers an important prognostic value in the clinical decision-making process, especially for the future as alternative emitters or administration schedule may become available., Competing Interests: Declarations. Ethics approval: The study was conducted following the Declaration of Helsinki and approved by the local ethical committee (protocol name & number: LUTADOSE, INT 28/20). Consent to participate: All patients provided written informed consent at the time of PRRT. Competing interests: Matteo Bauckneht reports personal fees from AAA and General Electric Healthcare outside the submitted work. Federica Scalorbi declares personal fees from AAA outside the submitted work. Carlo Chiesa received a fee as speaker at an online meeting by AAA. Marco Maccauro was supported by AAA for congress fee and he received an honorarium as consultant. The other authors do not report any conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maspero, Sposito, Bongini, Cascella, Flores, Maccauro, Chiesa, Niger, Pietrantonio, Leoncini, Bellia, Bhoori and Mazzaferro.)

Background: Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option., Methods: We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99., Results: Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy., Conclusion: Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile., Competing Interests: Declaration of Competing Interest All other authors declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Rectal neuroendocrine tumors (rNENs) are rare, constituting 1-2% of rectal tumors, and are often asymptomatic, leading to challenges in early diagnosis. Current management guidelines recommend endoscopic resection for small lesions and surgical intervention for larger or high-risk tumors. This study aims to retrospectively analyze the pathological characteristics, management, and prognosis of rNEN patients., Methods: Data from the Neuroendocrine Tumor Registry at a tertiary hospital in Milan, Italy from 2005 to 2023 were retrospectively analyzed. Patient demographics, disease characteristics, pathology findings, treatment details, and surveillance data were collected. Statistical analyses included descriptive statistics, multivariable binary logistic regression, and Kaplan-Meier survival analysis., Results: Forty-five patients were included, 53.3% male with a mean age of 57.5 years. Most patients were asymptomatic, with incidental diagnosis during colonoscopy. Endoscopic excision was the primary treatment modality (77.8%), with surgical resection reserved for incomplete or inappropriate endoscopic resections. Disease progression occurred in 13 patients (28.9%), with tumor-related mortality of 22.2%. Kaplan-Meier analysis showed 5- and 10-year survival rates of 68.8% and 59.1%, respectively, with corresponding progression-free survival rates of 72.8% and 54.0%. Tumor stage was significantly associated with disease progression on multivariable analysis (OR = 7.230, p = 0.039)., Conclusions: This study highlights the heterogeneous presentation and prognosis of rNENs, with a substantial proportion diagnosed incidentally. Endoscopic management was predominantly utilized, aligning with current guidelines for localized tumors. Tumor stage emerged as a significant predictor of disease progression, emphasizing the importance of accurate staging for optimal management. Further research is warranted to refine management protocols and validate these findings.

This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response., (© 2024. The Author(s).)

Introduction: To evaluate the role of unilateral inguinal lymph-node dissection (ILND) plus contralateral dynamic sentinel node biopsy (DSNB) vs. bilateral ILND in clinical N1 (cN1) penile squamous cell carcinoma (peSCC) patients., Material and Methods: Within our institutional database (1980-2020, included), we identified 61 consecutive cT1-4 cN1 cM0 patients with histological confirmed peSCC who underwent either unilateral ILND plus DSNB (26) or bilateral ILND (35)., Results: Median age was 54 years (Interquartile range [IQR]: 48-60 years). Median follow-up was 68 months (IQR 21-105 months). Most patients had pT1 (23 %) or pT2 (54.1%), as well as G2 (47.5%) or G3 (23%) tumors, while lymphovascular invasion (LVI) was present in 67.1% of cases. Considering a cN1 and a cN0 groin, overall 57 out of 61 patients (93.5%) had nodal disease in the cN1 groin. Conversely, only 14 out of 61 patients (22.9%) had nodal disease in the cN0 groin. 5-year IR-free survival was 91% (Confidence interval [CI] 80%-100%) for bilateral ILND group and 88% (CI 73%-100%) for the ipsilateral ILND plus DSNB group (P-value 0.8). Conversely, 5-year CSS was 76% (CI 62%-92%) for bilateral ILND group and 78% (CI 63%-97%) for the ipsilateral ILND plus contralateral DSNB group (P-value 0.9)., Conclusions: In patients with cN1 peSCC the risk of occult contralateral nodal disease is comparable to cN0 high risk peSCC and the gold standard, namely bilateral ILND, may be replaced by unilateral ILND and contralateral DSNB without affecting positive node detection, IRRs and CSS., Competing Interests: Conflict of Interest Nicola Nicolai certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0)., Methods: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients)., Results: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively., Conclusions: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The need for axillary dissection (AD) is declining, but it is still essential for many patients with nodal involvement who risk developing breast-cancer-related lymphedema (BCRL) with lifelong consequences. Previous nonrandomized studies found axillary reverse mapping and selective axillary dissection (ARM-SAD) a safe and feasible way to preserve the arm's lymphatic drainage., Methods: The present two-arm prospective randomized clinical trial was held at a single comprehensive cancer center to ascertain whether ARM-SAD can reduce the risk of BCRL, compared with standard AD, in patients with node-positive breast cancer. Whatever the type of breast surgery or adjuvant treatments planned, 130 patients with nodal involvement met our inclusion criteria: 65 were randomized for AD and 65 for ARM-SAD. Twelve months after surgery, a physiatrist assessed patients for BCRL and calculated the excess volume of the operated arm. Lymphoscintigraphy was used to assess drainage impairment. Self-reports of any impairment were also recorded., Results: The difference in the incidence of BCRL between the two groups was 21% (95% CI, 3-37; p = .03). A significantly lower rate of BCRL after ARM-SAD was confirmed by a multimodal analysis that included the physiatrist's findings, excess arm volume, and lymphoscintigraphic findings, but this was not matched by a significant difference in patients' self-reports., Conclusions: Our findings encourage a change of surgical approach when AD is still warranted. ARM-SAD may be an alternative to standard AD to reduce the treatment-related morbidity., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)