scholarly journals Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab

2016 ◽  
Vol 34 (13) ◽  
pp. 1510-1517 ◽  
Author(s):  
F. Stephen Hodi ◽  
Wen-Jen Hwu ◽  
Richard Kefford ◽  
Jeffrey S. Weber ◽  
Adil Daud ◽  
...  

Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

2020 ◽  
Vol 16 (20) ◽  
pp. 1441-1453
Author(s):  
Eric D Whitman ◽  
Emilie Scherrer ◽  
Wanmei Ou ◽  
Clemens Krepler

Aim: To determine outcomes of retreatment with anti-PD-1 monotherapy for melanoma. Materials & methods: This retrospective study included adults with unresectable cutaneous melanoma who achieved stable disease (SD) or better after anti-PD-1 monotherapy and were retreated with anti-PD-1 monotherapy after ≥90-day gap. We determined overall survival and real-world tumor response. Results: For 21 eligible patients, from retreatment initiation, median follow-up was 14.4 months (range, 2.6–34.5); median overall survival was 30.0 months (95% CI: 14.4–not reached); 1-year survival was 100% (95% CI: 100–100%); 2-year survival was 83% (48–96%). Of 16 patients with recorded best real-world tumor response, ten (63%) responded (complete/partial response); three achieved SD; three had progressive disease. Conclusion: Patients with advanced melanoma achieving SD/better after first-course anti-PD-1 monotherapy may benefit from retreatment.


2020 ◽  
Vol 8 (1) ◽  
pp. e000146 ◽  
Author(s):  
Flora Mulkey ◽  
Marc R Theoret ◽  
Patricia Keegan ◽  
Richard Pazdur ◽  
Rajeshwari Sridhara

BackgroundResponse criteria developed when cytotoxic chemotherapy was the predominant therapeutic modality to treat patients with cancer, do not capture the full spectrum of tumor response patterns observed with anti-PD-1/PD-L1 antibody treatment. iRECIST was developed to capture both typical and atypical response patterns.MethodsTarget, non-target, and new lesion measurements for 7920 patients receiving anti-PD-1/PD-L1 antibody (n=4751) or anti-CTLA-4 antibody (n=613) or undergoing chemotherapy (n=2556) from 14 randomized controlled trials submitted to the U.S. Food and Drug Administration were used to calculate the best overall response, objective response rate and progression-free survival (PFS) per iRECIST (iPFS) and Response Evaluation Criteria in Solid Tumours (RECIST). Associations between either PFS or iPFS and overall survival (OS) were evaluated using the method adopted by Obaet al.1ResultsAmong 4751 anti-PD-1/PD-L1-antibody treated patients, 31.5% (95% CI 30.2% to 32.9%) and 30.5% (95% CI 29.2% to 31.8%) achieved an objective response per iRECIST or RECIST V.1.1, respectively. OS among the 48 patients with objective response by iRECIST only resembled that in patients with responses per RECIST V.1.1. The association between iPFS and OS was R2=0.277 and that between PFS and OS was R2=0.260.ConclusionsPatients treated with anti-PD-1/PD-L1 antibodies with initial progressive disease per RECIST V.1.1 can experience prolonged stability or substantial reductions in tumor burden per iRECIST, atypical response patterns associated with prolonged OS. In the subgroup of patients with atypical responses, the application of iRECIST retrospectively in the evaluation of the objective response durations and the magnitude of PFS results in large differences compared with RECIST V.1.1. For the overall pooled population, the magnitude of these differences was modest, although a large proportion of patients had no further tumor assessments following RECIST V.1.1-defined progressive disease. Prospective studies employing iRECIST will be required to assess whether this response criteria more fully captures the benefit of immune checkpoint inhibitors.


2020 ◽  
Vol 13 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Angelo Castello ◽  
Egesta Lopci

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Methods: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1041
Author(s):  
Jun Nakata ◽  
Kayako Isohashi ◽  
Yoshihiro Oka ◽  
Hiroko Nakajima ◽  
Soyoko Morimoto ◽  
...  

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4878-4878
Author(s):  
Byeong Seok Sohn ◽  
Eun Kyoung Kim ◽  
Dok Hyun Yoon ◽  
Myoung Joo Kang ◽  
Dae Ro Choi ◽  
...  

Abstract Abstract 4878 Introduction According to international uniform response criteria for multiple myeloma suggested in 2006, the response assessment for patients with oligo- and non-secretory multiple myeloma (MM) can be evaluated by the serum free light chain (FLC) assay. Although the FLC response criteria are not applicable in MM patients with measurable disease, there were several reports suggesting that serial measurement of serum FLC may detect relapse earlier than protein electrophoresis studies. We, therefore, investigated the preceding changes in serial serum FLC assay until progressive disease was confirmed by the international uniform response criteria in post-ASCT patients with measurable disease. Patients and Method We included patients from the AMC MM transplant registry, who met the following (1) undertook ASCT for measurable disease (2) showed, at least, two serial response assessment of stable disease or complete response before progression or relapse by serum or urine M-protein, (3) had periodic serum FLC assay simultaneously tested with serum and/or urine protein electrophoresis at each response assessment. Progressive disease (PD) was defined by increase of ≥ 25% from baseline in serum M-protein (the absolute increase must be ≥ 0.5mg/dL) and/or urine M-component (the absolute increase must be ' 200mg/24h) according to international uniform response criteria. In this investigation, significant increase in the difference between involved and uninvolved FLC (dFLC) and in the involved FLC (iFLC) was defined by increase of ≥ 25% from baseline. The positive predictive value of three cutoff levels for absolute increase, 10mg/L, 20mg/L, 100mg/L, were evaluated for both dFLC and iFLC provided serum FLC ratio was abnormal. Each patient was followed up with 1-3 month intervals according to the protocol for MM patients after ASCT. Result A total 29 patients of 138 patients in the AMC MM transplant registry satisfied above criteria. When the cut-off level for absolute increase was defined as 100mg/L, the significant increase of iFLC in 12 patients (41%) and dFLC in 11 patients (38%) preceded or accompanied with the time of progressive disease observed by M-protein. The median value of preceding time was 2 month (range -5 - 0). When the cut-off level was defined as 20mg/L, the sustained significant increase of iFLC in 21 patients (72%) and dFLC in 17 patients (59%) preceded or accompanied with the time of progressive disease with median of 2 month (range -9 - 0) and 2 month (range, -5 – 0), respectively. At the cut-off level of 10mg/L, the sustained significant increase of iFLC in 23 patients (79%) and dFLC in 21 patients (72%) preceded or accompanied with the time of progressive disease observed by M-protein. The median of preceding time was 2 month (range -11 - 0) and 1 month (range, -11 - 0), respectively. Twenty-eight dFLC values were observed as negative values out of a total 123 data from 29 patients. Of these values, 12 were below normal iFLC concentration, 14 within normal range of iFLC (kappa 8.5 - 23.7 mg/L, lambda 9.5 - 23.5 mg/L), and 2 above normal iFLC concentration. Conclusion In this study, about 70% of patients showed sustained significant increase of iFLC that preceded or accompanied the time of progressive disease observed by M-protein by a median of 2 months at a cut-off absolute increase of 20mg/L. Although there is a subtle difference in prediction rates according to defined cut-off levels, serial follow up of iFLC and sustained increase by 25% during follow-up seems to have a utility in the prediction of progression after ASCT. In addition, interpretations of dFLC may be difficult as it is frequently observed as negative value in post-ASCT MM patients. Therefore, the serial and sustained increase of iFLC may be useful in lower iFLC concentrations. However, there should be more validation with large patients' population. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1772-1772
Author(s):  
Santiago Pavlovsky ◽  
Astrid Pavlovsky ◽  
Isolda Fernandez ◽  
Miguel Pavlovsky ◽  
Virginia Prates ◽  
...  

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3665-3665
Author(s):  
Harumi Kato ◽  
Takeshi Kodaira ◽  
Kazuhito Yamamoto ◽  
Yukihiko Oshima ◽  
Yasuhiro Oki ◽  
...  

Abstract Abstract 3665 Background: Chemoradiotherapy is considered as one of standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). Involved-node radiation therapy (IN-RT) is a newly defined concept for patients with early Hodgkin lymphoma. However, there are as yet few reports of applying the strategy to DLBCL and the optimal radiation treatment fields for patients with limited-stage DLBCL have not been well defined. We conducted a retrospective study to evaluate efficacy and long-term toxicities in limited-stage DLBCL patients receiving IN-RT or involved-field radiation therapy (IF-RT) plus short-course chemotherapy. Patients and Methods: Subjects were consecutive patients newly diagnosed as limited-stage DLBCL and receiving local radiation therapy after short-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or R-CHOP (rituximab-CHOP) chemotherapy in our institute from 1993 to 2010. Each patient underwent CT simulation for treatment planning and decided to receive either IN-RT or IF-RT regarding diagnostic imaging after chemotherapy including FDG-PET or PET-CT. The concept of IFRT included the whole initially involved lymph node regions according to the Ann Arbor staging diagram. IN-RT was defined as radiation therapy fields that encompass the initially involved lymph nodes exclusively and to encompass their initial volume with adequate margin less than 3 cm. Results: A total of 108 patients were identified, of which 70 patients received IF-RT. The median age was 62 years (range: 19 to 81). Twelve patients (11%) had bulky disease (≥ 5cm). Baseline patients' characteristics were given in Table 1. There was no statistically difference in risk factors as defined by the stage-modified International Prognostic Index score (IPI) between the two groups (P= 0.25). Most patients (94%) received three courses of chemotherapy (range: 2 to 4). Median dose of radiation was 40Gy (range: 23.4 to 51.2). With a median follow-up of 5.5 years (range: 0.35–17), the 5-year overall survival rates were 94% (95%CI: 87 to 97) in all 108 patients, and 94% (95%CI: 79 to 99) and 94% (94%CI: 84 to 98), in the groups of IN-RT and IF-RT, respectively (P=0.76). Estimated 5-year overall survival rates in patients undergoing IF-RT plus CHOP or R-CHOP were 92% and 94%, respectively (P=0.65). Estimated 5-year overall survival rates in patients treated with IN-RT plus CHOP or R-CHOP were 88% and 100%, respectively (P=0.10). Four patients in the IF-RT group experienced relapses [median: 1.8 years after the start of therapy (range: 0.9 to 7.6)], on the other hand, no patient had relapse in the IN-RT group. Three out of the four patients had three adverse risk factors as defined by the stage-modified IPI. Two patients had the relapsed diseases outside radiation fields. Cumulative incidence of relapse at 5 year was 0% and 4.6% (95%CI: 1.2 to 12) in the patients receiving IN-RT and IF-RT, respectively (P= 0.13). During long-term follow-up, a total of nine patients (8%) developed solid cancer, including skin (n=2), lung (n=2), breast (n=1), gastric (n=2) and bladder (n=2). Seven of which occurred outside radiation fields. No patients developed secondary MDS/AML. Cumulative incidence of secondary malignancy at 5 year was 2.7% (95%CI: 0.20 to 12) and 9.5 % (95%CI: 3.3 to 19) in the groups of IN-RT and IF-RT, respectively, and the cumulative incidence at 10 year was estimated to be 22% (95%CI: 4.0 to 49) and 23% (95%CI: 4.4 to 51) in the groups of IN-RT and IF-RT, respectively. There was no statistically difference in the occurrence of secondary malignancy between the two treatment arms. (P=0.70). Conclusions: IN-RT with short-course CHOP or R-CHOP chemotherapy could be expected as good as IF-RT in terms of local disease control and could produce excellent survival rates. However, incidence of secondary malignancy in patients receiving IN-RT was not decreased compared to that of IF-RT and the incidence was estimated to have been gradually increased until after 10 years. Physicians might consider the development of follow-up programs for patients with DLBCL undergoing chemoradiotherapy. Overall survival according to types of irradiation. The 5-year overall survival rates in patients receiving involved-node (IN-RT) and involved-field radiation therapy (IF-RT) were 94% (95%CI: 79 to 99) and 94% (94%CI: 84 to 98), respectively (p=0.76). Disclosures: Kinoshita: Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria.


2015 ◽  
Vol 6 (4) ◽  
pp. 13-18
Author(s):  
Svetlana Aleksandrovna Kulyova ◽  
Andrei Petrovich Karitsky ◽  
Svetlana Viacheslavovna Ivanova

Background. Calculation of relative tumor burden in Hodgkin’s lymphoma patients is the simplest and significant parameter which can be used in daily clinical practice as a risk factor. The aim of study was the assessment of influence of relative tumor burden on the late results of a disease. Material and methods. This research included data on 126 patients with Hodgkin’s lymphoma aged from 0 till 18 years (middle age of 11 years), treated risk-adapted treatment according to the DAL-HD and SPBLH-05. Boys was 70, girls - 56 (a ratio 1,25 : 1). Fifty-eight patients (46 %) are stratified in favorable risk group, 50 (39,7 %) - in intermediate risk group, and 50 (39,7 %) are included in unfavorable risk group. Results. Overall survival at 5 years was 93 % (range 91-95 %), event-free survival - 88 % (85-91 %). The average relative tumor burden was 129,4 cm3/m2 (7-609,7 cm3/m2). When carrying out ROC-analysis value of 122,7 cm3/m2 (р ˂ 0,0001) appeared the critical parameter, which worsen the prognosis of a disease. Overall survival in a patients cohort with this volume was 69,6 %, with the volume less than 122,7 cm3/m2 overall survival was 97,2 % (р = 0,00002). Conclusions. The relative tumor burden is the parameter which is significantly reducing survival rates in children with Hodgkin’s lymphoma. Opinion on interrelation of clinical and laboratory parameters with “sarkoma’s saturation” or tumor volume as end result of immunological frustration, it is represented the most perspective direction of studying of Hodgkin’s lymphoma.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9005-9005 ◽  
Author(s):  
A. C. van Akkooi ◽  
P. Rutkowski ◽  
I. M. van der Ploeg ◽  
C. A. Voit ◽  
H. J. Hoekstra ◽  
...  

9005 Background: Many studies have identified Sentinel Node (SN) tumor burden as a prognostic factor for additional non- SN (NSN) positivity and / or disease-free (DFS) and melanoma specific survival (MSS). It remains unclear if pts with minimal SN tumor burden can safely be managed without Completion Lymph Node Dissection (CLND). Pts with minimal SN tumor burden might be at risk for late recurrences (> 5 years). Methods: Slides of 595 SN positive patients were reviewed for this pan-European study collaboration in 5 major centers. Slides were reviewed for the microanatomic location and SN tumor burden according to the Rotterdam Criteria (< 0.1mm, 0.1 - 1.0mm and > 1.0 mm) for the maximum diameter of the largest metastasis. MSS, DFS and distant metastasis-free survival (DMFS) rates were calculated, as was NSN positivity. Results: In 595 SN positive pts, the mean and median Breslow thickness was 4.73 and 3.5 mm. Ulceration was present in 51% of melanomas. 67 pts had metastases < 0.1 mm (11%), 226 pts (38%) had 0.1 - 1.0 mm metastases and 302 pts had metastases > 1.0 mm (51%). Mean and median follow-up was 48 and 40 months for all patients (range 1 - 172). Patients with metastases < 0.1 mm had mean and median follow-up of 61 and 57 months, 46% (31pts) had follow up > 5 years and 25% (17 pts) had follow-up longer than 80 months (range 3 - 132). 5-year MSS rates were 94% for metastases < 0.1 mm, 70% for 0.1 - 1.0 mm and 57% for > 1.0 mm (p<0.001). 5-year DMFS rate was 91% for metastases < 0.1 mm. NSN positivity occurred in 5% of < 0.1mm, 17% of 0.1 - 1.0 and 29% of metastases > 1.0 mm (p<0.001). Conclusions: This large multicenter experience (n=595) has demonstrated that long-term follow-up of melanoma patients with minimal SN tumor burden (< 0.1 mm) indicates very low relapse rates and excellent MSS, seemingly identical to SN negative patients. With prolonged follow-up, an increase in the occurrence of relapses of any kind between 5 and 10 years follow up has not been identified, and excellent 10-year survival rates are expected. No significant financial relationships to disclose.


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