Predictive Factors of Non-Response to Vismodegib in Locally Advanced Basal-Cell Carcinoma

Dermatology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Hélène Marescassier ◽  
Léa Dousset ◽  
Marie Beylot-Barry ◽  
Philippe Célérier ◽  
Loïc Vaillant ◽  
...  
Keyword(s):  
Basal Cell ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Complete Response ◽  
Response To Treatment ◽  
Treatment Modalities ◽  
Muscle Involvement ◽  
Patient Demographics ◽  
History Of

<b><i>Background:</i></b> Vismodegib has shown clinical efficacy in the management of locally advanced basal cell carcinomas (laBCC). However, non-response to vismodegib is observed in 2–13.5% of patients in clinical studies. The purpose of this study was to identify factors associated with non-response to vismodegib in patients with laBCC. <b><i>Methods:</i></b> We carried out a retrospective multicenter study, including patients with laBCC treated with vismodegib, from July 2011 to May 2019. Response to treatment was assessed according to the RECIST 1.1 criteria. Patients were categorized as responders with a complete response or a partial response or non-responders with a stable disease or a progressive disease according to what has been observed during follow-up. Patient demographics, tumor profile, and treatment modalities were compared in responders and non-responders. <b><i>Results:</i></b> Eighty-three patients with laBCC were included in the study. Twenty-five (30.1%) were non-responders to vismodegib. History of treatment with radiotherapy, presence of muscle involvement and intermittent treatment with vismodegib were significantly associated with a non-response (<i>p</i> &#x3c; 0.001, <i>p</i> = 0.025, <i>p</i> &#x3c; 0.001). Bone involvement (<i>p</i> = 0.2) and morpheaform IaBCC subtype (<i>p</i> = 0.056) were more frequent in non-responders without reaching statistical significance. <b><i>Conclusion:</i></b> In this study, non-response of laBCC to vismodegib therapy was associated with muscle involvement. Previous radiotherapy and intermittent use of vismodegib have been identified as causes favoring non-response to vismodegib. Due to the low numbers of patients included in the study, it is difficult to draw firm conclusions. Further studies are needed to confirm these data.

Pathologic complete response to standard preoperative chemoradiation in patients with locally advanced rectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 686-686
Author(s):  
Madiha Naseem ◽  
Joshua Murray ◽  
Christine E. Simmons ◽  
Nancy Baxter ◽  
Marcus J. Burnstein ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Response To Treatment ◽  
Significant Response ◽  
Free Survival

686 Background: Pathologic complete response (pCR) is associated with lower rates of recurrences and longer disease-free survival rates in locally advanced rectal cancer (LARC) patients. The purpose of this study was to evaluate clinical outcomes of neoadjuvant chemoradiation and pCR among these patients. Methods: A retrospective chart review was performed for all patients treated for LARC between August 2005 and May 2011 at St. Michael's Hospital, Toronto. Patients were stratified into pCR and no-pCR groups and compared with respect to tumor size, nodal status, and treatment characteristics. Descriptive statistics were calculated for all variables of interest. Chi-square and t-tests were conducted to test for associations between categorical and continuous variables respectively. Disease free survival was calculated as the time between diagnosis and recurrence date, censored at last follow up. Results: A total of 92 patient charts were reviewed; 21 patients had metastatic carcinoma and were excluded from analysis. 63.4% (45/71) were male, with a mean age of 61.2 years and median follow up of 15 months. 12.7% (9/71) of patients achieved a pCR, while the remaining 87.35% (62/71) were no-pCR. All pCR patients received and completed standard pre-operative chemotherapy-radiotherapy. 73.4% (52/71) of the patients had complications from chemoradiotherapy. Furthermore, there was a significant association between having a significant response to treatment and achieving a pCR; where 78% (7/9) of pCR patients had a significant response to treatment. Overall, 4/71 patients had a local recurrence, 22.2% (2/9) pCR and 3.2% (2/62) no-pCR. Those with no-pCR had a recurrence at 1 and 2.2 years post diagnosis, while those with pCR had a recurrence at 3.7 years. Conclusions: This study suggests that patients undergoing standard pre-operative chemoradiotherapy are likely to have a significant response and achieve a pCR. Based on this study, although a pCR does not prevent the risk of recurrence, it delays the onset of local recurrence. Longer follow-up is required to determine if these results are robust and to develop future studies to improve efficacy of treatment delivery in LARC patients.

Ocular preservation with neoadjuvant vismodegib in patients with locally advanced periocular basal cell carcinoma

2018 ◽  
Vol 103 (6) ◽  
pp. 775-780 ◽  
Author(s):  
Oded Sagiv ◽  
Priyadharsini Nagarajan ◽  
Renata Ferrarotto ◽  
Thomas J Kandl ◽  
Sudip D Thakar ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Locally Advanced ◽  
Complete Response ◽  
Prolonged Treatment ◽  
Residual Tumour ◽  
8Th Edition

Background/AimsLocally advanced (T4 per American Joint Committee on Cancer (AJCC) 8th edition) periocular basal cell carcinoma (BCC) can lead to loss of the eye. We report the neoadjuvant use of vismodegib followed by surgery in patients with such lesions with eye preservation as primary goal.MethodsThis retrospective interventional study includes all patients with a T4 periocular BCC (per 8th edition AJCC for eyelid carcinoma) treated by the senior author between 2013 and 2017 with neoadjuvant vismodegib prior to definitive surgery.ResultsEight patients had a T4 tumour. Six patients presented with recurrent disease. Indications for neoadjuvant treatment were an unresectable tumour in one patient, an attempt to avoid an orbital exenteration in six patients and an attempt to avoid disfiguring facial surgery in one patient. Patients were treated for a median of 14 months (range: 4–36 months). All patients underwent an eye-sparing surgery following neoadjuvant vismodegib and all final surgical margins were negative for tumour. Five patients had a complete response to vismodegib with no microscopic residual BCC found during surgery; three patients had a significant partial response with residual tumour found on pathology. At last follow-up, a mean of 18 (range: 6–43) months after surgery, all patients were off-vismodegib and alive without evidence of disease.ConclusionsNeoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was well tolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.

The role of radiotherapy for large and locally advanced non-melanoma skin carcinoma

2012 ◽  
Vol 12 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Chance Matthiesen ◽  
Christina Forest ◽  
J. Spencer Thompson ◽  
Salahuddin Ahmad ◽  
Terence Herman ◽  
...  
Keyword(s):  
Basal Cell ◽  
Locally Advanced ◽  
Complete Response ◽  
Non Melanoma Skin Cancer ◽  
Institutional Experience ◽  
Radiotherapy Alone ◽  
Significant Factors ◽  
Melanoma Skin

AbstractBackground: The role of radiotherapy for large and locally advanced non-melanoma skin cancer is unclear. In this report, we aimed to review our institutional experience with patients treated with radiation therapy for T2–T4 NMSC and analyze outcomes.Methods: Seventy patients and 85 lesions were reviewed who received radiotherapy. Fifty-six lesions (65.9%) were untreated, 17 (20.0%) recurrent, and 12 (14.1%) post-operative. Forty-three (50.6%) were staged T2, 20 (23.5%) T3, and 22 (25.9%) T4. Median follow-up was 20 months.Results: Thirty-nine living patients (59.0%) had no evidence of disease, of which 35 (89.7%) required no therapy following radiotherapy. Twenty-seven patients (41.0%) died, of which 10 deaths were attributed to disease progression. Achievement of complete response (CR) to all therapy and radiotherapy alone was, respectively, 95.3% and 86% for T2, 70% and 65% for T3, and 68.2% and 59.1% for T4. Statistically significant factors for CR included basal cell histology (p = 0.005) and tumour stage T2 (0.01).Conclusions: Radiotherapy for T2–T4 NMSC is effective. Basal cell histology and T2 are statistically favoured to achieve CR to radiotherapy alone.

scholarly journals Pattern of sub-clinical dysthyroidism in a postthyroidectomy cohort: Implications for supplementary treatment

2018 ◽  
Vol 23 (3) ◽  
pp. 95-99
Author(s):  
Ronald Kintu-Luwaga ◽  
Timothy Makumbi ◽  
Cathy Kilyewala ◽  
Jane O. Fualal
Keyword(s):  
Total Thyroidectomy ◽  
Prospective Cohort ◽  
Statistical Significance ◽  
Female Gender ◽  
P Value ◽  
Patient Demographics ◽  
Accurate Dose ◽  
History Of ◽  
Biochemical Testing

Background: Defective thyroid functioning is referred to as dysthyroidism. Despite incomplete thyroidectomy or thyroxine supplementation, post-thyroidectomy patients may still experience dysthyroidism. Many times, this may be sub - clinical. This study aimed to assess the prevalence and pattern of sub-clinical dysthyroidism following thyroid surgery. Methods: In this prospective cohort study, 40 patients were consecutively recruited following conventional thyroidectomy and followed up to 12months. All patients were euthyroid at surgery. At 12 months serum TSH, T4 and T3 levels were measured and the patients clinically assessed. The prevalence and pattern of dysthyroidism was analysed statistically against the patient demographics, clinical and peri-operative variables for significance, using stata version 13. The confidence interval was at 95% and the statistical significance at a p-value of <0.05. Results: The mean age was 44.3 years (M:F= 1: 12.3). 20% of the patients had medical comorbidities. The types of surgery performed were sub-total thyroidectomy (55%), near total thyroidectomy (25%) and total thyroidectomy (20%). The prevalence of postoperative dysthyroidism was 52.5%. 22.7% of patients who underwent sub-total thyroidectomy had dysthyroidism. Most patients (90%) who were on thyroxine supplement (following total or near total thyroidectomy) still developed dysthyroidism (P= 0.017). The type of resection done had the greatest significance (P= 0.000). Other factors associated with dysthyroidism albeit non-significantly were history of pre-operative hyperthyroidism, middle age (40 - 60 years), and female gender. Conclusions: The prevalence of dysthyroidism in this cohort was high which may reflect the broader picture among post - thyroidectomy patients in this setting. Regular biochemical testing in post-thyroidectomy patients is important to identify and correct dysthyroidism early. This requires frequent follow-up and accurate dose adjustment, based on objective assessments like weight or body mass index. Keywords: post-thyroidectomy; dysthyroidism; hypothyroidism; hyperthyroidism; sub-clinical dysthyroidism; prospective; cohort 

scholarly journals 209 Breast Lymphoma Treatment Outcomes in a Pakistani Population: 20 Years of Experience at a Single Centre

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
M Abid ◽  
R Bano ◽  
A I Khan ◽  
S A Fiaz ◽  
M Z Chaudry ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Complete Response ◽  
Treatment Modalities ◽  
Single Centre ◽  
Pakistani Population ◽  
Patient Demographics ◽  
Breast Lymphoma ◽  
Lymphoma Treatment ◽  
The Mean

Abstract Background Breast lymphomas constitute a rare disease entity. To date, limited relevant data have been reported. We therefore here present a review of breast lymphoma patients treated at a single centre over 20-year period, focusing on histological types, treatment modalities and outcomes. Method We identified patients who were diagnosed and treated for breast lymphoma at a single centre from January 1995 to January 2014 and extracted data regarding patient demographics and clinical data. Results Twenty-seven patients with breast lymphoma were identified, of which 3 were males. Median age at diagnosis was 37 years (range:22-76 years). Chemotherapy was main stay of treatment and 55.6% patients also received radiation to affected breast. At our institute, only 3 patients, all with progressive disease, had surgery performed to achieve local palliation. Complete response after chemotherapy was seen in 63% patients and partial response in 7.4%, while 26% patients demonstrated disease progression. The mean follow up was 46.8 months. Seven patients (33.3%) who were alive at last follow up, as well as 1 patient who died, survived more than 5 years after diagnosis. Conclusions Patients with breast lymphoma should receive aggressive treatment, with combination of chemotherapy and radiation therapy. Surgery should be limited for diagnosis and palliation of local symptoms in cases of progressive disease.

scholarly journals Eosinophilic esophagitis: clinical features, endoscopic findings and response to treatment

2018 ◽  
Vol 5 (4) ◽  
pp. 1514
Author(s):  
Manoranjan U. D. ◽  
Nikhil S. ◽  
Divyarani M. N. ◽  
Akhila N. T.
Keyword(s):  
Eosinophilic Esophagitis ◽  
Controlled Trial ◽  
Response To Treatment ◽  
Treatment Modalities ◽  
Common Symptom ◽  
Inflammatory Disorder ◽  
Endoscopic Findings ◽  
History Of ◽  
Study Population

Background: Eosinophilic esophagitis (EoE) considered to be an allergic inflammatory disorder of the esophagus characterised by an inherent impairment in epithelial barrier integrity, possibly worsened by reflux of gastric contents. The aim of this study was to study EoE and its clinical and endoscopic evaluation and response to treatment with relapse rates.Methods: Fifty patients in the study were selected based on a review of biopsy results from previous endoscopies performed between August 2015 to August 2017. All patients with biopsy-proven EoE, defined as more than 20 eosinophils/HPF. Biopsy samples were taken from the mid and distal esophagus and sent for analysis. The endoscopic findings were noted grossly. Twenty five patients were started on PPI’s only and the remaining 25 patients were started on fluticasone MDI 440mcg inhaled two times day and PPI. Follow up of the patients was done at 1, 3 and 6 months after treatment.Results: The mean age in the study population was 42 years, males affected more often (64%) with rings and corrugations and linear furrows being the most commonly seen endoscopic findings (64% and 27%). Normal study was seen in 40% of the patients. Most common symptom was dysphagia 26%. Steroids are the mainstay of the treatment along with PPI. Relapse rate was 61.1% in the study.Conclusions: EoE is an inflammatory condition of the oesophagus that occurs predominantly in young and middle-aged men, EE should be strongly considered in those who present with dysphagia and/or food impaction, particularly with a history of atopic disorders. Swallowed fluticasone is a safe and effective treatment; however, relapse rates are very high. In adults, there remains a need for a randomized controlled trial to assess the safety and efficacy of various treatment modalities. 

scholarly journals Sialendoscopy With Intraductal Steroid Irrigation in Patients With Sialadenitis Without Sialoliths

2019 ◽  
Vol 98 (5) ◽  
pp. 291-294 ◽  
Author(s):  
Saudamini J. Lele ◽  
Mickie Hamiter ◽  
Torrey Louise Fourrier ◽  
Cherie-Ann Nathan
Keyword(s):  
Treatment Option ◽  
Case Series ◽  
Complete Response ◽  
Definitive Treatment ◽  
Invasive Technique ◽  
Effective Treatment Option ◽  
Patient Reported ◽  
History Of ◽  
The Mean

Sialendoscopy has emerged as a safe, effective and minimally invasive technique for management of obstructive and inflammatory salivary gland disease. The aim of our study was to analyze outcomes of sialendoscopy and steroid irrigation in patients with sialadenitis without sialoliths. We performed a retrospective analysis of patients who underwent interventional sialendoscopy with steroid irrigation from 2013 to 2016, for the treatment of sialadenitis without sialolithiasis. Twenty-two patients underwent interventional sialendoscopy with ductal dilation and steroid irrigation for the treatment of sialadenitis without any evidence of sialolithiasis. Conservative measures had failed in all. Eleven patients had symptoms arising from the parotid gland, 4 patients had symptoms arising from the submandibular gland, while 6 patients had symptoms in both parotid and submandibular glands. One patient complained of only xerostomia without glandular symptoms. The mean age of the study group which included 1 male and 21 females was 44.6 years (range: 3-86 years). Four patients had autoimmune disease, while 7 patients had a history of radioactive iodine therapy. No identifiable cause for sialadenitis was found in the remaining 11 patients. The mean follow-up period was 378.9 days (range: 16-1143 days). All patients underwent sialendoscopy with ductal dilation and steroid irrigation. Twelve patients showed a complete response and 9 patients had a partial response, while 1 patient reported no response. Only 3 patients required repeat sialendoscopy. The combination of sialendoscopy with ductal dilation and steroid irrigation is a safe and effective treatment option for patients with sialadenitis without sialoliths refractory to conservative measures. Prospective studies with a larger case series are needed to establish its role as a definitive treatment option.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Efficacy of local treatments in Prurigo Pigmentosa after Bariatric surgery

2021 ◽  
Vol 07 (02) ◽  
pp. 01-03
Author(s):  
Mezoun Almuhaimeed
Keyword(s):  
Bariatric Surgery ◽  
Clinical Presentation ◽  
Response To Treatment ◽  
Single Female ◽  
Provisional Diagnosis ◽  
Patient Response ◽  
Medical City ◽  
History Of ◽  
Multivitamin Supplements

A 22-year-old single female presented to primary care Wazarat Health Center at Prince Sultan Military Medical City in Riyadh, with a 3 weeks history of itchy erythematous papules and vesicles and papulo-vesicles over the neck, chest, and upper back and face, which started 4 to 5 days after bariatric surgery. The patient on daily multivitamin supplements, vitamin D (50,000 IU, weekly / 2 months). The patient has lost 4kg since the operation, family history of atopy was positive regarding the mother physical examination shows erythematous papules and vesicles and papulo-vesicles over the neck with crust, chest, and upper back, Based on medical history and clinical presentation a provisional diagnosis was Prurigo Pigmentosa. The patient was prescribed topical mometasone furoate cream (BID for one week). Two -week follow-up showed improvement of the eruption. The course of the disease was shorter than usual in such cases the patient response to treatment was reactive to the topical mometasone without taking the oral minocyline, which major of such cases need in the late course of the disease The patient starts to improve within 2 weeks compared to others who need an average of 6 weeks to improve in such cases

scholarly journals Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3115-3121 ◽  
Author(s):  
Bart Barlogie ◽  
Mauricio Pineda-Roman ◽  
Frits van Rhee ◽  
Jeff Haessler ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Complete Remission ◽  
Statistical Significance ◽  
Complete Response ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Prognostic Feature ◽  
Total Therapy ◽  
Initiation Of Therapy ◽  
The One

AbstractTotal Therapy 2 examined the clinical benefit of adding thalidomide up-front to a tandem transplant regimen for newly diagnosed patients with multiple myeloma. When initially reported with a median follow-up of 42 months, complete response rate and event-free survival were superior among the 323 patients randomized to thalidomide, whereas overall survival was indistinguishable from that of the 345 patients treated on the control arm. With further follow-up currently at a median of 72 months, survival plots segregated 5 years after initiation of therapy in favor of thalidomide (P = .09), reaching statistical significance for the one third of patients exhibiting cytogenetic abnormalities (CAs; P = .02), a well-recognized adverse prognostic feature. The duration of complete remission was also superior in the cohort presenting with CAs such that, at 7 years from onset of complete remission, 45% remained relapse-free as opposed to 20% on the control arm (P = .05). These observations were confirmed when examined by multivariate analysis demonstrating that thalidomide reduced the hazard of death by 41% among patients with CA-positive disease (P = .008). Because two thirds of patients without CAs have remained alive at 7 years, the presently emerging separation in favor of thalidomide may eventually reach statistical significance as well.

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