- Email: [email protected]
EXTENT OF THYROIDECTOMY FOR PAPILLARY THYROID CANCER. WILL THE CONTROVERSY EVER END?
THURSDAY, FEBRUARY 24,201 1
Symposium Symposium 1 : Thyroid Cancer 5 speaker EXTENT OF THYROIDECTOMY FOR PAPILLARY THYROID CANCER. WILLTHE CONTROVERSY EVER END? M. Hamoirl UCL CLINIQUESUNIV. ST.LUC,Brussels, Belgium Abstract not received
6 speaker MINIMALLY INVASIVE VIDEO-ASSISTED THYROIDECTOMY (MIVAT) P. Miccolil UNIVERSITY OF PISA, Surgery, Pisa, Italy The first report of a videoscopic access to the neck was described by Gagner in 1996 and was immediately followed by the introduction of several other techniques. Minimally lnvasive Video-Assisted Parathyroidectomy (MIVAP) for the treatment of Primary Hyperparathyroidism (PHPT) has been introduced in 1996 in our Department, and described one year later. Since then, several reports have demonstrated the significant advantages of the technique. Immediately after the MIVAP, the Minimally lnvasive Video-Assisted Thyroidectomy (MIVAT) was also set up in our Department in 1998. The procedure is based on the same median incision of the MIVAP, 2 cm above the sternal notch, and relies as well on the same external retraction. More than 2000 thyroidectomies have been performed with this technique since June 1998, and the main indications for surgery are: undetermined thyroid nodules less than 3 cm, and papillary thyroid cancers less than 2 cm in their largest diameter. The mean operative time for a lobectomy is 32.3 (range 20-120) minutes, while it is 44.1 (30-130) minutes for total thyroidectomy. Mean time for videoassisted prophylactic central compartment lymphadenectomy is 57 min. Conversion to standard cervicotomy was required in 2.2% of the cases and operative complications were represented by transient unilateral recurrent nerve palsy in 2.6%. A definitive unilateral recurrent nerve palsy was recorded in 1.1% of the whole series. A transient hypoparathyroidism was recorded in 4.2% of the total thyroidectomies performed, but only 2 cases demonstrated a permanent hypoparathyroidism. Discussion We find it appropriate to cluster all interventions on the thyroid where the surgeon is using an endoscope, either during the full intervention or part of it, under the term "endoscopic thyroid/parathyroidectomy or video-assisted technique". Several prospective studies comparing conventional thyroid and parathyroid surgery performed through a minimally invasive incision to endoscopic techniques have clearly shown a less postoperative pain and better cosmetic results with endoscopic techniques. From our own experience, we judge the use of endoscopic techniques superior because they provide a greater and better surgical image, with magnification of all anatomical structures normally encountered in conventional open surgery. The operative time, after an acceptable learning curve, is comparable to that of the conventional technique, and the possibility given by the central access to treat both uni- and bilateral thyroid diseases should not be underestimated, especially in endemic goiter countries such as Italy. Moreover, the possibility of radically treating low or intermediate risk thyroid cancers has been clearly demonstrated in literature, and represents another further advantage for this type of surgery. Even if there is a great hype behind the robot-assisted thyroidectomy, a technique that looks perfectly indicated in the treatment of low and intermediate risk differentiated thyroid cancers, we still cannot include it between the minimally invasive techniques, due to the extensive dissection it actually needs: the future will arguably see the possibility of using a robotassisted technique from other and less extended approaches than the axilla. 7 speaker TARGETED THERAPY IN REFRACTORY THYROID CANCER M. Schlumbergerl INSTITUT GUSTAVE Roussv, Villejuif, France The majority of patients with differentiated thyroid carcinoma (DTC) or medullary thyroid carcinoma (MTC) can be cured, others may survive for decades despite persistent disease, and few patients may require novel therapeutic modalities. These refractory thyroid cancer patients are rare, with an estimated annual incidence in France of 350 cases. In most patients, an initiating carcinogenic event can be found and molecular targeted therapy may thus be given on a rational basis. Patients should preferably be included in prospective trials, and even phase Itrials that are testing the newest therapies should be considered for patients with progressive thyroid cancer, as these
SYMPOSIUM
s7
protocols may allow early identification of possibly effective drugs. Although response criteria in these contemporary trials differ markedly from those evaluating cytotoxic chemotherapy, anti-tumor efficacy of these agents in MTC patients is likely to be much greater than that of earlier chemotherapies. It appears that response rates are similar in lymph nodes, and lung, liver and bone metastases. Comparison of the outcome among these compounds is at the present time not possible. Toxicity was significant and should limit their use to patients with progressive or symptomatic disease and those with large tumor burden. Benefits demonstrated with vandetanib on both ORR and PFS counterbalance toxic effects and justify its use in such MTC patients. Results of the ongoing phase 111 trial with XL-184 are expected to confirm promising results obtained in the phase I trial. There is apparently no cross resistance between drugs. Drugs used up to now have similar mechanisms of action, all being anti-angiogenic and some targeting the RET tyrosine kinase. The relative role of the inhibition of each target or of their combined inhibition is currently unknown, but because axitinib and pazopanib are thought to be only anti-angiogenic drugs, responses suggest an important role for the antiangiogenic effects of these compounds. Also, responses to vandetanib or XL-184 have been observed in patients without RET mutation. Even among patients with a RET mutation, tumor responses were partial and were observed in only a fraction of patients. This may indicate that targeting RET may not be sufficient in all MTC tumors. Future studies should explore the interest of effective inhibition of the MAPkinase pathway downstream the RET kinase and of other pathways such as the P13K-AKT-mTOR pathway, and search for other relevant targets that may indicate the use of other drugs. In DTC patients, refractory disease is defined as the presence of at least one tumor focus without any uptake of radioiodine, or by progressive disease following radioiodine treatment or by persistent disease after 6 treatments with radioiodine. Among these cancers, histology (papillary and variants, follicular and poorly differentiated) and genetic defects may differ. Anti-tumor efficacy of these agents is likely to be greater than that of earlier chemotherapieswith partial responses observed in 8-32% of patients and long-term stable disease in at least another half. Comparison of the outcome among these compounds is at the present time not possible, but the recent response rate reported with pazopanib seems higher than in previous reports. It also appears that efficacy may differ among histological subtypes, but further studies are needed to correlate drug efficacy to the genetic defect present in the tumor. Only results of phase II trials have been reported; a phase 111 trial (sorafenib vs placebo) is ongoing and at least two phase 111 trials will be activated in 201 1, as well as several phase IItrials. Also, the stability of response and patterns of relapse have not been well characterized. Drugs used up to now have similar mechanisms of action, all being anti-angiogenic and some targeting the kinase in the MAPkinase pathway. Tumor responses were partial and transient and were observed in only a fraction of patients. This may indicate that future studies should use drugs targeted to already known abnormalities (such as the mutated BRAF), and search for other relevant targets. Given the commercial availability of sorafenib and sunitinib, these agents have entered clinical use for those patients with progressive, refractory disease who are not suitable candidates for clinical trials. Further trials should also search in MTC and DTC patients for other treatment modalities, including combination or sequential treatment. Recent trials have shown that inclusion of the expected number of thyroid cancer patients to reach statistically significant conclusions is possible in a limited period of time, and this may be improved by networks such as the french TUTHYREF network and organizations such as the EORTC.
Symposium Symposium 1 : Thyroid Cancer 5 speaker EXTENT OF THYROIDECTOMY FOR PAPILLARY THYROID CANCER. WILLTHE CONTROVERSY EVER END? M. Hamoirl UCL CLINIQUESUNIV. ST.LUC,Brussels, Belgium Abstract not received
6 speaker MINIMALLY INVASIVE VIDEO-ASSISTED THYROIDECTOMY (MIVAT) P. Miccolil UNIVERSITY OF PISA, Surgery, Pisa, Italy The first report of a videoscopic access to the neck was described by Gagner in 1996 and was immediately followed by the introduction of several other techniques. Minimally lnvasive Video-Assisted Parathyroidectomy (MIVAP) for the treatment of Primary Hyperparathyroidism (PHPT) has been introduced in 1996 in our Department, and described one year later. Since then, several reports have demonstrated the significant advantages of the technique. Immediately after the MIVAP, the Minimally lnvasive Video-Assisted Thyroidectomy (MIVAT) was also set up in our Department in 1998. The procedure is based on the same median incision of the MIVAP, 2 cm above the sternal notch, and relies as well on the same external retraction. More than 2000 thyroidectomies have been performed with this technique since June 1998, and the main indications for surgery are: undetermined thyroid nodules less than 3 cm, and papillary thyroid cancers less than 2 cm in their largest diameter. The mean operative time for a lobectomy is 32.3 (range 20-120) minutes, while it is 44.1 (30-130) minutes for total thyroidectomy. Mean time for videoassisted prophylactic central compartment lymphadenectomy is 57 min. Conversion to standard cervicotomy was required in 2.2% of the cases and operative complications were represented by transient unilateral recurrent nerve palsy in 2.6%. A definitive unilateral recurrent nerve palsy was recorded in 1.1% of the whole series. A transient hypoparathyroidism was recorded in 4.2% of the total thyroidectomies performed, but only 2 cases demonstrated a permanent hypoparathyroidism. Discussion We find it appropriate to cluster all interventions on the thyroid where the surgeon is using an endoscope, either during the full intervention or part of it, under the term "endoscopic thyroid/parathyroidectomy or video-assisted technique". Several prospective studies comparing conventional thyroid and parathyroid surgery performed through a minimally invasive incision to endoscopic techniques have clearly shown a less postoperative pain and better cosmetic results with endoscopic techniques. From our own experience, we judge the use of endoscopic techniques superior because they provide a greater and better surgical image, with magnification of all anatomical structures normally encountered in conventional open surgery. The operative time, after an acceptable learning curve, is comparable to that of the conventional technique, and the possibility given by the central access to treat both uni- and bilateral thyroid diseases should not be underestimated, especially in endemic goiter countries such as Italy. Moreover, the possibility of radically treating low or intermediate risk thyroid cancers has been clearly demonstrated in literature, and represents another further advantage for this type of surgery. Even if there is a great hype behind the robot-assisted thyroidectomy, a technique that looks perfectly indicated in the treatment of low and intermediate risk differentiated thyroid cancers, we still cannot include it between the minimally invasive techniques, due to the extensive dissection it actually needs: the future will arguably see the possibility of using a robotassisted technique from other and less extended approaches than the axilla. 7 speaker TARGETED THERAPY IN REFRACTORY THYROID CANCER M. Schlumbergerl INSTITUT GUSTAVE Roussv, Villejuif, France The majority of patients with differentiated thyroid carcinoma (DTC) or medullary thyroid carcinoma (MTC) can be cured, others may survive for decades despite persistent disease, and few patients may require novel therapeutic modalities. These refractory thyroid cancer patients are rare, with an estimated annual incidence in France of 350 cases. In most patients, an initiating carcinogenic event can be found and molecular targeted therapy may thus be given on a rational basis. Patients should preferably be included in prospective trials, and even phase Itrials that are testing the newest therapies should be considered for patients with progressive thyroid cancer, as these
SYMPOSIUM
s7
protocols may allow early identification of possibly effective drugs. Although response criteria in these contemporary trials differ markedly from those evaluating cytotoxic chemotherapy, anti-tumor efficacy of these agents in MTC patients is likely to be much greater than that of earlier chemotherapies. It appears that response rates are similar in lymph nodes, and lung, liver and bone metastases. Comparison of the outcome among these compounds is at the present time not possible. Toxicity was significant and should limit their use to patients with progressive or symptomatic disease and those with large tumor burden. Benefits demonstrated with vandetanib on both ORR and PFS counterbalance toxic effects and justify its use in such MTC patients. Results of the ongoing phase 111 trial with XL-184 are expected to confirm promising results obtained in the phase I trial. There is apparently no cross resistance between drugs. Drugs used up to now have similar mechanisms of action, all being anti-angiogenic and some targeting the RET tyrosine kinase. The relative role of the inhibition of each target or of their combined inhibition is currently unknown, but because axitinib and pazopanib are thought to be only anti-angiogenic drugs, responses suggest an important role for the antiangiogenic effects of these compounds. Also, responses to vandetanib or XL-184 have been observed in patients without RET mutation. Even among patients with a RET mutation, tumor responses were partial and were observed in only a fraction of patients. This may indicate that targeting RET may not be sufficient in all MTC tumors. Future studies should explore the interest of effective inhibition of the MAPkinase pathway downstream the RET kinase and of other pathways such as the P13K-AKT-mTOR pathway, and search for other relevant targets that may indicate the use of other drugs. In DTC patients, refractory disease is defined as the presence of at least one tumor focus without any uptake of radioiodine, or by progressive disease following radioiodine treatment or by persistent disease after 6 treatments with radioiodine. Among these cancers, histology (papillary and variants, follicular and poorly differentiated) and genetic defects may differ. Anti-tumor efficacy of these agents is likely to be greater than that of earlier chemotherapieswith partial responses observed in 8-32% of patients and long-term stable disease in at least another half. Comparison of the outcome among these compounds is at the present time not possible, but the recent response rate reported with pazopanib seems higher than in previous reports. It also appears that efficacy may differ among histological subtypes, but further studies are needed to correlate drug efficacy to the genetic defect present in the tumor. Only results of phase II trials have been reported; a phase 111 trial (sorafenib vs placebo) is ongoing and at least two phase 111 trials will be activated in 201 1, as well as several phase IItrials. Also, the stability of response and patterns of relapse have not been well characterized. Drugs used up to now have similar mechanisms of action, all being anti-angiogenic and some targeting the kinase in the MAPkinase pathway. Tumor responses were partial and transient and were observed in only a fraction of patients. This may indicate that future studies should use drugs targeted to already known abnormalities (such as the mutated BRAF), and search for other relevant targets. Given the commercial availability of sorafenib and sunitinib, these agents have entered clinical use for those patients with progressive, refractory disease who are not suitable candidates for clinical trials. Further trials should also search in MTC and DTC patients for other treatment modalities, including combination or sequential treatment. Recent trials have shown that inclusion of the expected number of thyroid cancer patients to reach statistically significant conclusions is possible in a limited period of time, and this may be improved by networks such as the french TUTHYREF network and organizations such as the EORTC.