Retrospective review of patients treated with intensity modulated radiation therapy (IMRT) with or without concurrent chemotherapy for locally advanced thyroid cancer: The Dana-Farber experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16060-e16060
Author(s):  
Swati Kodali ◽  
Sewanti Atul Limaye ◽  
Aditya V. Shreenivas ◽  
Dave Zhao ◽  
Jochen H. Lorch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Local Control ◽  
Locally Advanced ◽  
Medullary Carcinoma ◽  
Concurrent Chemotherapy ◽  
Anaplastic Carcinoma ◽  
Regional Control ◽  
Locally Recurrent ◽  
Advanced Thyroid Cancer

e16060 Background: Chemotherapy has been used concurrently with radiation for local control as adjuvant treatment or for locally recurrent thyroid cancer. We present our experience using IMRT with or without sensitizing concurrent chemotherapy in this setting. Methods: All patients with thyroid carcinoma with or without minimal metastatic disease treated since 2005 at DFCI were reviewed. We collected data and analyzed the outcomes of patients treated with IMRT with or without concurrent chemotherapy for local control. Results: Twenty-two patients were identified: 13 Males, 9 Female, Median age 60 years There were 11 papillary, 6 medullary, 4 anaplastic, and1 follicular. Thirteen patients were treated adjuvantly, seven for locally recurrent disease and two definitively for unresectable disease. All patients with papillary and follicular thyroid cancer had prior surgery and radioactive iodine therapy. Patients with medullary carcinoma had surgery alone. Two patients with anaplastic carcinoma had surgery and two were found to be unresectable.. Seventeen patients received concurrent weekly carboplatin AUC1.5 and paclitaxel 30mg/m2 with radiation. Five patients did not receive any concurrent chemotherapy and were treated with radiotherapy alone. Radiation fields encompassed the thyroid bed, bilateral neck and in some cases the mediastinum. The radiation dose ranged from 5600cGy to 6600cGy. Mean follow up was 42 months. The overall survival at 36 months was 89.5% (95% CI, 76.7-100). Two patients with unresectable anaplastic thyroid cancer died from progressive disease. Loco-regional control rate at 36 months was 78.9% (95% CI, 62.6-99.6). No grade 3 or 4 toxicities were reported during treatment. Conclusions: IMRT with or without concurrent chemotherapy provided excellent loco regional control and might have contributed to improved overall survival in patients with locally advanced thyroid cancer.

Management of Advanced Thyroid Cancer: Anaplastic Carcinoma.

2001 ◽  
Vol 52 (2) ◽  
pp. 149-153
Author(s):  
Katsuhiro Hirakawa ◽  
Koji Yajin ◽  
Takaharu Tatsukawa
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Carcinoma ◽  
Advanced Thyroid Cancer

scholarly journals Role of interstitial brachytherpy using template (mupit) in locally advanced carcinoma cervix

2016 ◽  
Author(s):  
Ashish Bhange ◽  
Abhishek Gulia ◽  
Anirudh Punnakal ◽  
Anil Kumar Anand ◽  
Anil Kumar Bansal ◽  
...  
Keyword(s):  
Local Control ◽  
Residual Disease ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Interstitial Brachytherapy ◽  
Carcinoma Cervix ◽  
Advanced Carcinoma ◽  
Needle Position ◽  
Grade 3

Introduction: Locally advanced carcinoma cervix includes stages IIB, IIIA, IIIB and IVA. Interstitial brachytherapy has the potential to deliver adequate dose to lateral parametrium and to vagina. Hence, it is preferable in cases with distorted anatomy, extensive (lower) vaginal wall involvement, bulky residual disease post EBRT and parametrium involvement upto lateral pelvic wall. Aim and Objective: To determine clinical outcome and complications (acute and chronic) in locally advanced carcinoma cervix, treated with interstitial brachytherapy using template (MUPIT - Martinez universal perineal interstitial template). Materials and Methods: This study is a retrospective analysis of 37 cases of locally advanced carcinoma cervix (stage IIB-2, IIIB-30, IVA-5), treated with EBRT (dose-median 45Gy/25#) ± concurrent chemotherapy (CCT) - Inj. Cisplatin/Inj Carboplatin, followed by interstitial brachytherapy using MUPIT from December 2009 to June 2015. Initial treatment with EBRT ± CCT was followed by intertstitial brachytherapy. Under spinal anaesthesia and epidural analgesia, MUPIT application was done. Straight and divergent needles (median 26, range 19-29) were inserted to cover parametrium adequately. Needle position was verified with planning CT scan and Brachytherapy planning was done. Dose was normalized to 5 mm box surface from outermost needle with optimization of dose to OAR (Bladder, Rectum and Sigmoid colon). Prescription dose –25Gy in 5#. Treatment was delivered by Microselectron HDR using Ir192 source. Treatment fractions were delivered twice daily with min 6 Hrs. gap in-between fractions. Results: The median duration of follow-up was 25 months. Local control was achieved in 28 patients with residual disease in 7 patients and local recurrence in 2 patients. 10 patients had acute lower GI toxicity {Grade1 (n=6), Grade 2 (n=4)}, 2 patients had acute Grade 1 bladder toxicity. 1 patient had grade 3 and 1 patient had grade 4 chronic bladder toxicity. Chronic rectal toxicity was seen in 10 patients {Grade 2 (n=4), Grade 3 (n=4), Grade 4 (n=2)}. Conclusion: Local control was achieved in 28/37 patients (75.6%) and overall survival rate of 81.1% at median follow up of 25 months in patients with locally advanced carcinoma cervix and unfavorable prognostic factors.

scholarly journals Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2867 ◽  
Author(s):  
Woo Lee ◽  
Seul Lee ◽  
Seung Yim ◽  
Daham Kim ◽  
Hyunji Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Exome Sequencing ◽  
Papillary Thyroid Cancer ◽  
Whole Exome Sequencing ◽  
Primary Tumor ◽  
Tumor Heterogeneity ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Whole Exome ◽  
Advanced Thyroid Cancer

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Does time to completion of radiation treatment in locally advanced vulvar cancer impact survival?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5593-5593
Author(s):  
Nancy T. Nguyen ◽  
Xiao Zhao ◽  
Matthew Ponzini ◽  
Machelle Wilson ◽  
Gary S. Leiserowitz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Vulvar Cancer ◽  
Radiation Treatment ◽  
Locally Advanced ◽  
Group Versus ◽  
Figo Stage ◽  
Concurrent Chemotherapy ◽  
Stage Ii ◽  
Event Analysis

5593 Background: Although well established in cervical cancer, it is unclear whether time from initiation to completion of radiation therapy for vulvar cancer affects survival outcomes. We seek to assess if completion of radiation, either alone (RT) or as concurrent chemoradiation (CRT), within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). Methods: Women 18 years or older with FIGO stage II to IVA vulvar cancer who received external beam RT or CRT as part of their initial treatment course were identified from the National Cancer Database from 2004-2017. Patients with non-squamous cell carcinoma histology or who received systemic cytotoxic therapies as primary treatment were excluded. Patients who received less than 20 fractions of radiation were also excluded. Time to radiation completion was the number of days from the initiation to completion of radiation. The delay of radiation completion was calculated as the difference between the actual time to radiation completion and predicted duration of radiation. Types of treatment (RT and CRT) were both stratified into groups based on the delay of radiation completion, less than 7 days or greater than 7 days. Chi-square, Fisher Exact ANOVA and Kruskal-Wallis tests were used for analysis. Kaplan-Meier curves with log-rank tests were fit for univariate time-to-event analysis. Multivariable Cox proportional hazard models were fit to assess effects after controlling for confounding. Results: There were 2378 patients identified for analysis (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78) and the CRT group was younger (p < 0.0001) than the RT group. The majority were white (88.35%) with advanced FIGO stage III or IVA (72.29 %) disease. Median dose of total radiation was 5720 cGy (IQR 5040-6300) with higher doses observed in the greater than 7 days delay group versus less than 7 days, (p < 0.0001). Median follow up was 27.2 (IQR 11.8-57.9) months. For both cohorts, completion of treatment with delay less than 7 days resulted in significant improvement in median survival when compared to treatment completion delay of more than 7 days: RT (Median OS 34.9 versus 21.6 months, p < 0.01) and CRT (58 versus 41.3 months, p < 0.01). On multivariate subset analysis, both completion of CRT and RT were associated with improved OS when treatment was completed with less than 7 days delay vs greater than 7 days delay, CRT (HR 0.869 [95%CI 0.758-0.997]), RT (HR 0.820 [95%CI 0.698-0.964]). Advanced FIGO stage IVA was associated with the greatest increase in hazard of death, (HR 1.758 [95%CI 1.516-2.039]), compared to FIGO stage II. Conclusions: Completion of radiation with less than 7 days delay is associated with improved overall survival, which is independent of concurrent chemotherapy. These findings suggest that strategies to minimize delays in radiation treatment are crucial in treating locally advanced vulvar cancer.

Resection and surgically targeted radiation therapy for locally recurrent GBM.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2054-2054
Author(s):  
David Brachman ◽  
Peter Nakaji ◽  
Kris Smith ◽  
Theresa Thomas ◽  
Christopher Dardis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Local Control ◽  
Local Treatment ◽  
Post Hoc Analysis ◽  
Locally Recurrent ◽  
Targeted Radiation Therapy ◽  
Post Hoc ◽  
Recurrent Gbm

2054 Background: Recurrent GBM (rGBM) is a diffuse disease, and resection (R) alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing R plus immediate radiation (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we prospectively evaluated R combined with a novel surgically targeted radiation therapy (STaRT) device utilizing Cs-131 embedded in bioresorbable collagen tiles. Methods: From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm trial (ClinicalTrials.gov, NCT#03088579) of maximum safe resection and immediate RT (GammaTile, GT Medical Technologies, Tempe AZ). Upon resection the at-risk areas of the surgical bed were lined with the GammaTile (GT) device, delivering 60-80 Gy at 5 mm. Follow up treatments were not specified but captured; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present study specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of outcomes by receipt of systemic (Sys) therapy. Results: 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range.1-42.3), and radiographic LC was 8.8 mo. (range.01-34.5). LC (defined as < 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for > 50 yrs. (HR.46, p =.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received > 1 cycle of systemic therapy (Sys), either as adjuvant or salvage, alone or in combination . Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8 (N > 17 as some pts. received > 1 Sys). Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving > 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR).38, p =.017)). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR.44; p =.16)). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR.38, p =.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR.40, p =.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR.61, p =.25), respectively. Three attributed AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects, medically treated. 4 unrelated deaths occurred < 60 days post-op, all in the Sys- cohort, impacting their opportunity for subsequent treatment. Conclusions: In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+GT coupled with Sys may have potential to impact OS in rGBM patients. GT was FDA cleared in 2020 for use in newly diagnosed malignant and all recurrent intracranial neoplasms. Clinical trial information: NCT#03088579.

The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6069-6069
Author(s):  
Naisi Huang ◽  
Guohua Sun ◽  
Yulong Wang ◽  
Jiaying Chen ◽  
Qing Guan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Primary Treatment ◽  
Tumor Diameter ◽  
Efficacy And Safety ◽  
Advanced Thyroid Cancer

6069 Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.

Management of Locally Recurrent Sarcoma in the Extremity

2017 ◽  
Author(s):  
Lauren Krumeich ◽  
Madalyn G Neuwirth ◽  
Giorgos Karakousis
Keyword(s):  
Local Recurrence ◽  
Local Control ◽  
Malignant Tumors ◽  
Short Interval ◽  
Locally Advanced ◽  
Isolated Limb Perfusion ◽  
High Grade ◽  
Factors Associated ◽  
Limb Perfusion ◽  
Locally Recurrent

Extremity sarcomas are a heterogeneous group of malignant tumors with a varied propensity for local recurrence. This review focuses on factors associated with local recurrence and survival, diagnostic workup, management, outcomes, and surveillance. Local recurrence is more common in patients with previous local recurrence, positive margins, high-grade histology, and deep tumors. In the absence of metastases, the mainstay of treatment is limb-sparing surgery, with radiation to improve local control. Modalities such as brachytherapy or proton therapy may be valuable in the setting of previous irradiation. Systemic chemotherapy is typically limited to the treatment of distant disease, although chemotherapy can be delivered locally via limb perfusion or infusion for locally advanced or recurrent disease. Amputation is used if local control cannot be achieved while preserving adequate limb function or as a palliative option for pain, bleeding, or fungating tumors. Prognostic factors associated with poor survival include tumors that recur with high-grade histology, with a large size (> 5 cm), or within a short interval (< 16 months). Reports of 5-year overall survival in patients with locally recurrent sarcomas vary from 36 to 65%. Surveillance includes physical examination, cross-sectional imaging, and chest x-ray. Genetic profiling and intratumoral injections provide novel therapeutic targets. This review contains 1 figure, 4 tables and 40 references.   Key words: chemotherapy, hyperthermic isolated limb perfusion, intratumoral injection, isolated limb perfusion, local recurrence, margin status, radiation, soft tissue sarcoma, wide local excision 

Management of Locally Advanced Thyroid Cancer

2018 ◽  
pp. 85-95
Author(s):  
Andrea R. Marcadis ◽  
Jennifer Cracchiolo ◽  
Ashok K. Shaha
Keyword(s):  
Thyroid Cancer ◽  
Locally Advanced ◽  
Advanced Thyroid Cancer

A phase II study of axitinib (AG-013736 [AG]) in patients (pts) with advanced thyroid cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6008-6008 ◽  
Author(s):  
E. E. Cohen ◽  
E. E. Vokes ◽  
L. S. Rosen ◽  
M. S. Kies ◽  
A. A. Forastiere ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Thyroid Tumor ◽  
External Beam Radiation ◽  
Vegf Receptors ◽  
Beam Radiation ◽  
Thyroid Cancers ◽  
Advanced Thyroid Cancer ◽  
Multi Center Study

6008 Background: Elevated VEGF-A and VEGF-C have been reported in thyroid tumor tissue compared with normal thyroid. AG is a potent, small molecule inhibitor of VEGF receptors 1, 2 and 3. The efficacy and safety of AG therapy in pts with advanced thyroid cancers was examined in this single-arm, multi-center study. Methods: 60 pts with metastatic or unresectable locally-advanced thyroid cancer refractory to, or not suitable candidates for, 131iodine (131I) treatment, with measurable disease received AG at a starting dose of 5 mg orally BID. The primary endpoint was response rate (RR) by RECIST criteria. A Simon 2-stage minimax design was used (a=0.1; β=0.1; null RR=5%; alternative RR=20%). Samples were collected pretreatment and q8wks to explore relationships between clinical response and plasma soluble proteins. Results: Median age was 59 yrs (26–84), 35 (58%) were male. Histological subtypes included papillary: 29 pts (48%); follicular: 15 pts (25%)-11 (18%) with Hurthle cell variant; medullary: 12 pts (20%); anaplastic: 2 pts (3%), and other/unknown: 2 pts (3%). 53 pts (88%) had prior surgery, 42 (70%) had prior 131I treatment, 27 (45%) had prior external beam radiation, and 9 (15%) had prior chemotherapy. Partial response (PR) by investigator report was achieved in 13 pts (22% CI: 12.1, 34.2), with 31- 68% maximum tumor regression and duration of response (DOR) of 1–16 months. 30 pts (50%) have stable disease with a duration range of 4–13 months and 13–67% maximum tumor regression in 28 pts. Response assessments are ongoing. The treatment duration range is 6–670 days with 38 pts currently on study. Median PFS has not been reached with a median follow up of 273 days. The most common treatment-related adverse events were fatigue (37%), proteinuria (27%), stomatitis/mucositis (25%), diarrhea (22%), hypertension (20%) and nausea (18%). AG therapy consistently decreased soluble VEGFR2 and VEGFR3, and increased VEGF in the blood, demonstrating pharmacodynamic activity against targeted VEGF receptors. Conclusions: AG has substantial anti-tumor activity in advanced thyroid cancer with demonstrated pharmacodynamic activity. A global pivotal trial testing AG in doxorubicin refractory thyroid cancer is ongoing. [Table: see text]

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