Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4)

Forleo, Raffaella; Grani, Giorgio; Alfó, Marco; Zilioli, Valentina; Giubbini, Raffaele; Zatelli, Maria Chiara; Gagliardi, Irene; Piovesan, Alessandro; Ragni, Alberto; Morelli, Silvia; Puxeddu, Efisio; Pagano, Loredana; Deandrea, Maurilio; Ceresini, Graziano; Torlontano, Massimo; Puligheddu, B.; Antonelli, Alessandro; Centanni, Marco; Fugazzola, Laura; Spiazzi, Giovanna; Monti, Salvatore; Rossetto, Ruth; Monzani, Fabio; Tallini, Giovanni; Crescenzi, Anna; Sparano, Clotilde; Bruno, Rocco; Repaci, Andrea; Tumino, Dario; Pezzullo, Luciano; Lombardi, Celestino Pio; Petrillo, Umberto Ferraro; Durante, Cosimo; Castagna, Maria Grazia

doi:10.1089/thy.2021.0248

Cited by 16 publications

(6 citation statements)

References 28 publications

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“…A large retrospective analysis by Kim et al of 8297 intermediate-risk patients [ 59 ] failed to prove that RAI reduced the risk of loco-regional recurrence (HR = 0.852, p = 0.413), even in cases with additional negative features, such as larger tumor size, multifocality, mETE, lymph node metastases, and BRAF mutations. A longitudinal study of 470 PTC patients with mETE N0 or Nx found no significant difference in terms of a structural incomplete response at 1 year in patients treated with or without RAI [ 60 ], which was consistent with the results of a retrospective study with a smaller population but a longer follow-up period (median 7 years) [ 61 ]. Another study, based on the SEER registry showed some benefits in disease-specific survival, but only in particular subgroups, i.e., male gender ( p = 0.005), age > 45 years ( p < 0.001), and larger tumors ( p = 0.007) [ 62 ].…”

Section: Radioiodine Treatment Goalssupporting

confidence: 76%

Strategies for Radioiodine Treatment: What’s New

Sparano

Moog

Hadoux

et al. 2022

Cancers

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Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.

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Section: Radioiodine Treatment Goalssupporting

confidence: 76%

Strategies for Radioiodine Treatment: What’s New

Sparano

Moog

Hadoux

et al. 2022

Cancers

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“…Indeed, mETE has been associated with a slightly higher risk of recurrence [ 18 ], but this increase seems to be clinically irrelevant [ 19 ], and several authors have suggested that these tumours should be considered as low risk [ 20 ]. In a recent Italian observation-based study of a population with of low-to-intermediate risk DTCs, no differences were found in the response rates of patients with or without mETE [ 21 ]. Moreover, in other studies, mETE was ruled out as an independent predictive factor for response to RAI, especially in cases of pT1–pT2 staging and of local metastasis-free lesions [ 22 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…This outcome seems to be in open contradiction with established findings in the literature which consider the advancing of age as a negative predictive factor for tumour response. However, this issue is still the subject of live debate; indeed, in a recent work by Forleo et al, age at diagnosis was not revealed to be a factor that significantly impacts the outcome of intermediate-risk disease at one-year follow-up [ 21 ]. Still, an older age at diagnosis does appear to significantly raise the burden of mortality, as reported by a number of authors, including Kim et al, 2016 and Yan et al, 2018 and recently acknowledged by the AJCC in its VIII ed.…”

Section: Discussionmentioning

confidence: 99%

Post-Surgical Indications to Radioiodine Treatment and Potential Risk Factors for Post-Treatment Recurrence in Patients with Intermediate-Risk Differentiated Thyroid Carcinoma

Rossi

Mele

Giaccherino

et al. 2023

JPM

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In this multicentric retrospective observational study, we investigated the potential risk factors for radioiodine (RAI) indication and the post-treatment recurrence of intermediate-risk differentiated thyroid cancer (DTC) 1 and 3 years from diagnosis. We included 121 patients who underwent thyroidectomy for intermediate-risk DTC. The 92 patients (76.0%) who underwent RAI treatment had a higher prevalence of extra-thyroid micro-extension (mETE) (p = 0.03), pT3 staging (p = 0.03) and recourse to therapeutic central (p = 0.04) and lateral (p = 0.01) neck dissection, as well as higher numbers (p = 0.02) and greater dimensions (p = 0.01) of lymph node metastases, compared with untreated patients. Relapse was observed in 18.1% and 20.7% of cases 1 and 3 years from diagnosis, respectively, with no significant differences between groups. A lower age at diagnosis (p = 0.03) and higher levels of stimulated thyroglobulin (Tg) (p = 0.04) emerged as the only independent risk factors for tumour relapse at 1 year. Tumour relapse at 3 years was only independently predicted by the presence of tumour relapse at 1 year (p = 0.04). In conclusion, mETE, pT3 and the presence of large, multiple or clinically evident lymph node metastases represent the main indicators for referring patients to RAI treatment. Early recurrence may be considered the most relevant factor when planning further surveillance.

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“…Hay et al also found no difference in RFS between patients with mETE and no ETE [ 7 ]. More recently, Giorgio Grani et al conducted a retrospective study that failed to show the prognostic value of mETE in predicting initial therapy response, in a cohort of PTC patients without LNI, and the retrospective series of Weber et al found that mETE did not increase the risk for metastases at initial diagnosis and the recurrence rate [ 17 , 18 ]. In this last study, however, patients with mETE tended to be treated more aggressively: external beam radiation therapy was used more often higher median cumulative activities of RAI were used.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)

Bouzehouane

Roy

Decaussin‐Petrucci

et al. 2022

Cancers

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Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients treated by total thyroidectomy and radioactive iodine (RAI) with a five-year follow-up and tumors < 40 mm. In total, 303 patients were analyzed: 30.7% presented tumors with mETE, and 69.3% without. mETE was defined as extra-thyroidal invasion without skeletal muscle involvement. The primary outcome, DFS, was defined as the interval between initial treatment and any subsequent PTC-related treatment. The second outcome was the clinical status at five years. Results: In univariate analyses, the five-year DFS was significantly lower for tumors with mETE (62.4% versus 88.1%, p < 0.001). In multivariate analysis, mETE and massive lymph node involvement (LNI) were independent prognostic factors, associated respectively with a hazard ratio of 2.55 (95% CI 1.48–4.40) and 8.94 (95% CI 4.92–16.26). mETE was significantly associated with a pejorative clinical outcome at five years, i.e., biochemical/indeterminate response and structural persistence (Respectively OR 1.83 (95% CI 0.83; 4.06) and OR 4.92 (95% CI 1.87; 12.97)). Conclusion: Our results suggest that mETE is an independent poor prognosis factor of reduced DFS and predictive of poor clinical outcome.

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Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4)

Cited by 16 publications

References 28 publications

Strategies for Radioiodine Treatment: What’s New

Strategies for Radioiodine Treatment: What’s New

Post-Surgical Indications to Radioiodine Treatment and Potential Risk Factors for Post-Treatment Recurrence in Patients with Intermediate-Risk Differentiated Thyroid Carcinoma

Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)

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