Therapy For Metastatic Cancer Research Articles

Liver-Directed Therapy for Metastatic Colon Cancer: Update

Liver-Directed Therapy for Metastatic Colon Cancer: Update

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function.

NK cells play a crucial role in host protection during tumorigenesis. Throughout tumor development, however, NK cells become progressively dysfunctional through a combination of dynamic tissue-specific and systemic factors. While a number of immunosuppressive mechanisms present within the tumor microenvironment have been characterized, few studies have contextualized the spatiotemporal dynamics of these mechanisms during disease progression and across anatomical sites. Understanding how NK cell immunosuppression evolves in these contexts will be necessary to optimize NK cell therapy for solid and metastatic cancers. Here, we outline the spatiotemporal determinants of antitumor NK cell regulation, including heterogeneous tumor architecture, temporal disease states, diverse cellular communities, as well as the complex changes in NK cell states produced by the sum of these higher-order elements. Understanding of the signals encountered by NK cells across time and space may reveal new therapeutic targets to harness the full potential of NK cell therapy for cancer.

Сurrent options and perspectives of systemic therapy for advanced or metastatic adrenocortical cancer

Adrenocortical cancer is an orphan tumor with poor prognosis. The combination of EDP chemotherapy regimen and mitotane is the standard for the first‑line therapy. But there are no effective options for the second and consequent lines of therapy. The standard of second‑line therapy is the combination of gemcitabine, capecitabine and mitotane, which provides an objective response in 4–7 % of patients. Achievement of the therapeutic concentration of mitotane is the most important predictive factor of efficiency of GemCap + mitotane regimen, and, therefore, it is recommended to continue mitotane therapy after progression to mitotane. Recently, many researches regarding the efficiency of targeted and immunotherapy of adrenocortical cancer have been published. However, there are no standards for the third and subsequent lines of treatment. This review outlines the current views and perspectives of systemic therapy for advanced and metastatic adrenocortical cancer.

A case of hypopituitarism in a hemodialysis patient treated with nivolumab-ipilimumab combination therapy for metastatic renal cancer

症例は69 歳男性，腎硬化症にて2011 年血液透析導入された．左腎癌（淡明細胞型）に対して2020 年6 月開腹左腎摘除術を施行した．2021 年7 月のCT で多発肺転移巣を認め，IMDC リスク分類で中リスクであり，同年8 月より免疫チェックポイント阻害療法（ニボルマブ・イピリムマブ併用療法）を開始した．day 30 より急激な血圧低下を認め，ACTH，コルチゾール低下傾向にあり，day 35 よりヒドロコルチゾン20 mg/day 内服開始とした．まもなく血圧は安定しday 49 よりヒドロコルチゾンは10 mg/day に減量した．その後ACTH 負荷試験を施行，コルチゾールは正常反応を示し，副腎機能は保たれていた．また2 者（CRH・TRH）負荷試験では，CRH 負荷でACTH 低反応，コルチゾール無反応，TRH 負荷でTSH 無反応，プロラクチン低反応であった．他の下垂体前葉ホルモンも低下傾向にあり，汎下垂体機能低下症をきたしていると考えられた．治療効果に関しては3 コース施行後PR（partial response）を認め，5 コース施行後もPR を維持し主要病変は消失した．

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer

(Abstracted from N Engl J Med 2021;385:1856–1867) Platinum-based chemotherapy plus bevacizumab and paclitaxel is the standard first-line therapy for persistent, recurrent, or metastatic cervical cancer. The phase 2 KEYNOTE-158 trial found evidence of a response to pembrolizumab among patients with programmed death ligand-1 (PD-L1) positive cervical cancer.

Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis.

Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void. To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens. PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs. Overall, 3255 and 1452 patients were respectively included in the first- and second-line settings. In 1st line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2nd line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2nd line CT. In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1st line setting. However, pembrolizumab holds a survival benefit in 2nd line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.

Involvement of gold and silver nanoparticles in lung cancer nanomedicines: A review

The use of nanoparticles in cancer therapies has spawned a new field of study known as cancer nanomedicines. Gold and silver nanoparticles are advantageous in both diagnostic and therapies. It’s an astonishment to see the benefits and application of metal nanoparticles over traditional therapy. Its medications are more effective. Physical, chemical, and biological processes are used to make gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs). To destroy cancer cells, NPs grab incoming photons and change these into heat. AgNPs are primarily employed for antibacterial and anticancer therapy. In this article, we conclude with the uses of these nanoparticles as anti-cancer agents and the various methods through which they destroy cancer cells. Nanoparticle-based medicines are leading the way in primary and metastatic lung cancer diagnosis, imaging, screening, and therapies. This study covers recent accomplishments and obstacles in nanoparticle-based drug delivery systems with a focus on lung cancer therapy.

Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer Lacking Driver Mutations and Future Perspectives.

Simple SummaryThe following paper was developed as a reference for healthcare workers who are looking for information on advanced non-small cell lung cancers that lack driver mutations and their treatment with immunotherapy. The aim of the present study is to provide a reliable data source based on a review of the most current papers on the PD-1/PD-L1 and CTLA-4 inhibitors, as well as their use in medical practice.From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.

Two-Step Acoustophoresis Separation of Live Tumor Cells from Whole Blood.

There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluidic preseparation step to separate cells based on their acoustic mobility. This acoustofluidic step enriches viable cancer cells in a central outlet, but a significant number of white blood cells (WBCs) remain in the central outlet fraction due to overlapping acoustophysical properties of these viable cells. A subsequent purging step was employed to remove contaminating WBCs through negative selection acoustophoresis with anti-CD45-functionalized negative acoustic contrast particles. We processed 1 mL samples of 1:1 diluted RBC lysed whole blood mixed with 10 000 DU145 cells through the A2 method. Additional experiments were performed using 1000 DU145 cells spiked into 1.5 × 106 WBCs in 1 mL of buffer to further elucidate the dynamic range of the method. Using samples with 10 000 DU145 cells, we obtained 459 ± 188-fold depletion of WBC and 42% recovery of viable cancer cells. Based on spiked samples with 1000 DU145 cells, our cancer cell recovery was 28% with 247 ± 156-fold WBC depletion corresponding to a depletion efficacy of ≥99.5%. The novel A2 method provides extensive elimination of WBCs combined with the gentle recovery of viable cancer cells suitable for downstream functional analyses and in vitro culture.

First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer

BackgroundAdvanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.MethodsThis study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.ResultsSix patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.ConclusionsPalliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System.

FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GN) are established first line therapies for metastatic pancreatic cancer (MPC). There are, however, no randomized controlled trials comparing FFX and GN in the first line setting and real-world data on their comparative effectiveness is limited. We aimed to evaluate the outcomes of patients with MPC who were treated with first line FFX and GN and to further characterize dose modifications, discontinuation rates due to treatment toxicity, and rates of hospitalizations while on treatment. We manually abstracted data from the electronic medical records (EMR) system at Yale Smilow Hospital and Smilow Cancer Hospital Care Centers for patients with MPC treated with at least one cycle of first line FFX or GN from January 2011 to April 2019. Patients who received prior neoadjuvant or adjuvant FFX or GN and adjuvant gemcitabine less than 6 months prior to metastatic recurrence were excluded. The median time to treatment discontinuation (TTD) and overall survival (OS) were determined using Kaplan-Meier method. We identified 363 patients for analysis; 269 (74%) patients were treated with FFX and 94 (26%) with GN. Median TTD was 4.8 (IQR, 2.3-8.0) months in the FFX group compared to 3.4 (IQR, 1.3-5.7) months in the GN group (P=0.0037). Median OS was 11.3 (95% CI: 10.7-12.9) months in the FFX group and 7.0 (95% CI: 6.0-8.7) months in the GN group (P<0.001). Initial dose modifications occurred in 264 (98%) and 86 (91%) of FFX and GN treated patients, respectively (P=0.001). While on treatment, 56 (60%) of GN-treated patients had at least one hospitalization vs. 110 (41%) in the FFX-group (P=0.002). Treatment was discontinued due to chemotherapy toxicity in 26 (10%) and 14 (15%) among the FFX and GN cohorts, respectively (P=0.275). Patients treated with first line FFX had increased survival and TTD compared to patients treated with GN despite increased dose modifications and similar rates of treatment discontinuation due to treatment-related toxicity. GN-treated patients were older and more likely to be hospitalized while on treatment. Further study evaluating comparative effectiveness between these two regimens is warranted.

Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data.

Simple SummaryThis experimental preclinical study developed a strategy to identify signatures for the personalized treatment of colon cancer focusing on target-specific drug combinations. Tumor growth inhibition was analyzed in a preclinical phase II study using 25 patient-derived xenograft models (PDX) treated with drug combinations blocking alternatively activated oncogenic pathways. Results reveal an improved response by combinatorial treatment in some defined molecular subgroups and potential alternative treatment options in KRAS- and BRAF-mutated colon cancer.The current standard therapies for advanced, recurrent or metastatic colon cancer are the 5-fluorouracil and oxaliplatin or irinotecan schedules (FOxFI) +/− targeted drugs cetuximab or bevacizumab. Treatment with the FOxFI cytotoxic chemotherapy regimens causes significant toxicity and might induce secondary cancers. The overall low efficacy of the targeted drugs seen in colon cancer patients still is hindering the substitution of the chemotherapy. The ONCOTRACK project developed a strategy to identify predictive biomarkers based on a systems biology approach, using omics technologies to identify signatures for personalized treatment based on single drug response data. Here, we describe a follow-up project focusing on target-specific drug combinations. Background for this experimental preclinical study was that, by analyzing the tumor growth inhibition in the PDX models by cetuximab treatment, a broad heterogenic response from complete regression to tumor growth stimulation was observed. To provide confirmation of the hypothesis that drug combinations blocking alternatively activated oncogenic pathways may improve therapy outcomes, 25 models out of the well-characterized ONCOTRACK PDX panel were subjected to treatment with a drug combination scheme using four approved, targeted cancer drugs.

Locally advanced or oligometastatic bladder cancer-role of local treatment of the primary tumor and metastases

HintergrundDas muskelinvasive Blasenkarzinom stellt in seiner Behandlung eine besondere Herausforderung dar, da die Therapie mit signifikanten Nebenwirkungen und Komplikationsraten einhergeht, insbesondere bei Patienten mit relevanten Begleiterkrankungen. Im metastasierten Stadium besteht der Therapiezweck in der Palliation, wobei das Vorliegen einer Oligometastasierung eine gesonderte Rolle einnimmt. In diesem Stadium kann auch die Therapie des Primärtumors relevant sein, wenn die Metastasen neben einer systemischen Therapie ebenso lokal behandelt werden können – insbesondere auch in Hinblick auf die über die letzten Jahre die Therapielandschaft erweiternden neuen medikamentösen Möglichkeiten.Ziel der ArbeitIn diesem Reviewartikel sollen die Einflüsse einer definitiven Therapie des Primärtumors bei Patienten mit oligometastasiertem Urothelkarzinom der Harnblase dargelegt werden.Material und MethodenBasierend auf einer nicht-systemischen Literaturrecherche soll ein Überblick über bestehende Ergebnisse zur Therapie des oligometastasierten Blasenkarzinoms in Hinblick auf den Einfluss der Therapie des Primärtumors geben, wobei die Daten meist auf retrospektiven Studien und Metaanalysen bestehen.SchlussfolgerungEine Lokaltherapie des Primärtumors im Rahmen eines multimodalen Therapiekonzepts kann bei selektionierten Patienten mit lymphogen metastasiertem und oligometastasiertem Blasenkarzinom einen positiven Einfluss auf Überleben, Lebensqualität und Vermeidung von Lokalkomplikationen nehmen, wobei für die Wahl der lokalen Therapie dieselben Kriterien angewendet werden sollten wie im nicht-metastasierten Stadium.

The impact of DNA testing on management of patients with colorectal cancer.

Knowledge of the genetic basis of colorectal cancer has evolved over the past decades, allowing for the pre‐symptomatic identification of affected patients in those with familial syndromes and to the understanding of the multi‐step progression to carcinogenesis in tumors. Knowledge of the genes and pathways involved in colorectal cancer has allowed for targeted therapies in patients in addition to standard chemotherapy for those with metastases. Next‐generation sequencing technologies have now also allowed for the sensitive detection of circulating mutations derived from tumors, which can give insight into the presence of residual disease and has implications for changing the standard paradigms for treatment. This article will specifically review advances in targeted therapy in metastatic colon cancer and the progress being made in using circulating tumor DNA in patient management.

The role of stereotactic body radiation therapy and its integration with systemic therapies in metastatic kidney cancer: a multicenter study on behalf of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) genitourinary study group.

Although systemic therapy represents the standard of care for polymetastatic kidney cancer, stereotactic body radiation therapy (SBRT) may play a relevant role in the oligometastatic setting. We conducted a multicenter study including oligometastatic kidney cancer treated with SBRT. We retrospectively analyzed 207 patients who underwent 245 SBRT treatments on 385 lesions, including 165 (42.9%) oligorecurrent (OR) and 220 (57.1%) oligoprogressive (OP) lesions. Most common sites were lung (30.9%) for OR group, and bone (32.7%) for OP group. Among 78 (31.8%) patients receiving concomitant systemic therapy, sunitinib (61.5%) and pazopanib (15.4%) were the most common for OR patients, while sunitinib (49.2%) and nivolumab (20.0%) for OP patients. End points were local control (LC), progression free survival (PFS), overall survival (OS), time to next systemic therapy (TTNS) and toxicity. Median follow-up was 18.6months. 1, 2 and 3-year LC rates were 89.4%, 80.1% and 76.6% in OR patients, and 82.7%, 76.9% and 64.3% in those with OP, respectively. LC for OP group was influenced by clear cell histology (p = 0.000), total number of lesions (p = 0.004), systemic therapy during SBRT (p = 0.012), and SBRT dose (p = 0.012). Median PFS was 37.9months. 1, 2- and 3-year OS was 92.7%, 86.4% and 81.8%, respectively. Median TTNS was 15.8months for OR patients, and 13.9months for OP patients. No grade 3 or higher toxicities were reported for both groups. SBRT may be considered an effective safe option in the multidisciplinary management of both OR and OP metastases from kidney cancer.

Progress in treatment of PD-1/PD-L1 inhibitors for bladder cancer

Because of the limited effect of traditional treatment methods such as surgical treatment, radiotherapy and chemotherapy,the emergence of immunotherapy has brought new hope for the treatment of patients with bladder cancer. As an immune checkpoint inhibitor, programmed death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) inhibitor has shown good anti-tumor activity and safety in the treatment of advanced bladder cancer, and has been recommended for advanced bladder cancer as second-line treatment by NCCN guidelines. PD-1/PD-L1 inhibitor for the treatment of bladder cancer has covered the first-line and second-line treatment, as well as maintenance therapy after first-line chemotherapy of locally advanced or metastatic bladder cancer, adjuvant and neoadjuvant therapy of muscle-invasive bladder cancer, treatment of high-risk non-muscle invasive bladder cancer failed by Bacille Calmette-Guérin vaccine perfusion, and bladder preservation therapy of muscle-invasive bladder cancer. Some of related studies have achieved certain results, and some are in progress, both of which need to be further examined. Maybe it can provide new guidance and ideas for clinical treatment of bladder cancer.

Multimodality therapy in metastatic pancreas cancer with a BRCA mutation and durable long-term outcome: biology, intervention, or both?

ABSTRACT Metastatic pancreatic adenocarcinoma (PDAC) is a rapidly lethal disease, with less than half of patients surviving 12 months, and 5-year survival approximately 3%. These outcomes are in large part due to a lack of effective medical and surgical therapies for metastatic PDAC. Herein, we present the case of a patient with oligometastatic liver recurrence of BRCA2-mutated PDAC following a curative-intent resection. Through a combination of systemic chemotherapy, metastasectomy, radiotherapy, and subsequent targeted therapy with olaparib, the patient is asymptomatic four years following metastatic diagnosis with stable low-volume disease. This patient’s excellent outcome is attributable to the multi-disciplinary care received, all aspects of which were informed by new evidence surrounding metastasectomy for metastatic PDAC, the unique biology and medical treatment of BRCA-mutated PDAC, and the role of radiotherapy in controlling locoregional recurrence. We provide a review of this evidence, while highlighting the importance of evaluating disease biology through somatic and germline genetic testing as well as monitoring response to systemic chemotherapy.

Cost-Effectiveness of SABR in Oligometastatic Cancer: An Economic Analysis Based on Long-Term Results of the SABR-COMET Trial

<h3>Purpose/Objective(s)</h3> Our published economic analysis of the SABR-COMET randomized trial determined that SABR is cost-effective for patients with 1-5 oligometastases, with incremental cost-effectiveness ratios (ICERs) of $37,157 (2018 CAD$) and $54,564 (2018 USD$) for the Canadian and American health care systems, respectively. Long-term outcomes from SABR-COMET, with a median follow-up of 51 months, are now available. The aim of this study is to re-evaluate the cost-utility of SABR for oligometastatic cancers in the context of these new results. <h3>Materials/Methods</h3> The published Markov model was updated to perform a cost-utility analysis based on the long-term results of the SABR-COMET trial from the Canadian and American payer perspectives. Utility values and probabilities were derived from individual patient-level trial data. Costs were extracted from the published literature and adjusted to 2018 Canadian dollars and 2018 US dollars. Deterministic sensitivity analyses were performed to obtain thresholds at which each strategy would be preferred. Probabilistic sensitivity analysis was performed to assess the robustness of this model. A lifetime horizon was used with a cycle length of 3 months. A willingness-to-pay threshold of $100,000 in each respective currency, per quality-adjusted life year (QALY) was used. QALYs and costs were discounted at a rate of 1.5% and 3% for Canadian and American analyses, respectively. <h3>Results</h3> In the base case scenario, SABR was cost-effective at an ICER of $30,793 (CAD) and $48,370 (USD) per QALY gained. This finding was most sensitive to the difference in systemic therapy use (ICER: $25,051-48,021[CAD]; $36,319-69,096 [USD]), number of metastatic lesions treated with SABR (ICER: $22,702-44,709 [CAD]; $40,868-70,874 [USD]), and variation in general cancer care cost (ICER: $24,780-36,807 [CAD]; $38,377-58,362 [USD]). Probabilistic sensitivity analysis revealed that SABR was a cost-effective strategy in 99.9% of tested iterations. <h3>Conclusion</h3> This updated decision-analytic model suggests that SABR for patients with 1-5 metastatic lesions is more cost-effective than was initially estimated in both Canadian and the American health care systems. As systemic therapies for metastatic cancer are rapidly evolving, the efficacy and value of SABR with novel agents are currently undergoing further prospective evaluation.

Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia.

The aim of our retrospective study was to evaluate the outcome of patients with metastatic medullary thyroid cancer (MTC) treated with tyrosine kinase inhibitors (TKIs) and/or chemotherapy with the emphasis on analysis on the cohort treated by induction TKI because of locally advanced metastatic MTC. We analyzed the outcome of 30 patients (21 males, 9 females; median age 63.8years) with metastatic MTC treated between 2000-2020. Sunitinib was used in 20 patients. Median progression-free survival on TKI and on chemotherapy was 10.6 (95% CI7.1-14) months and 3.5 (95% CI1.4-5.5) months, respectively. Median overall survival from diagnosis and from metastasis presentation was 38.2 (95% CI 4.7-71.7)months and 20.9 (95% CI13.8-27.9)months, respectively. Eight patients (five females, three males; 58-86years of age, median age 70years) were treated with induction TKI because of inoperable locally advanced and metastatic MTC. The response rate to induction TKI was 50%; two patients (25%) had stable disease, and two patients (25%) had progressive disease. Our data support a new paradigm that TKIs may be the first treatment option in selected patients with locally advanced metastatic MTC, followed by locoregional treatment with surgery and/or external beam radiotherapy. Further studies are required to consolidate the presented data.