Time to completion of radiation treatment in locally advanced vulvar cancer and the impact on survival

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.

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The impact of positron emission tomography/computed tomography addition to contrast-enhanced computed tomography findings during radiation treatment planning of locally advanced carcinoma esophagus

Journal of Medical Physics ◽

10.4103/jmp.jmp_13_19 ◽

2019 ◽

Vol 44 (4) ◽

pp. 276

Author(s):

Shweta Sharma ◽

Sharad Bhatnagar ◽

Manoj Semwal ◽

Sankalp Singh

Keyword(s):

Computed Tomography ◽

Radiation Treatment ◽

Locally Advanced ◽

Radiation Treatment Planning ◽

Positron Emission ◽

Contrast Enhanced ◽

Carcinoma Esophagus ◽

Enhanced Computed Tomography ◽

The Impact ◽

Contrast Enhanced Computed Tomography

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Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience

Tumori Journal ◽

10.1177/03008916211027627 ◽

2021 ◽

pp. 030089162110276

Author(s):

Adorni Marco ◽

Bazzurini Luca ◽

Lissoni Andrea Alberto ◽

Vecchione Francesca ◽

Negri Serena ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Partial Response ◽

Vulvar Cancer ◽

Elderly Women ◽

Radical Surgery ◽

Locally Advanced ◽

Complete Response ◽

Tumor Burden ◽

Clinical Response Rate

Background: Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Methods: Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Results: Fourteen patients (93%) completed NACT with tolerable toxicities (G3–G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. Conclusion: NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.

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Proton beam radiotherapy of locally advanced or recurrent conjunctival squamous cell carcinoma: experience of the CATANA Centre

Journal of Radiotherapy in Practice ◽

10.1017/s1460396920000953 ◽

2020 ◽

pp. 1-8

Author(s):

Roberto Milazzotto ◽

Rocco Luca Emanuele Liardo ◽

Giuseppe Privitera ◽

Luigi Raffaele ◽

Vincenzo Salamone ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Proton Beam ◽

Squamous Cell ◽

Locally Advanced ◽

Disease Free Survival ◽

Proton Beam Radiotherapy ◽

Conjunctival Squamous Cell Carcinoma ◽

The Impact

Abstract Aim: Conjunctival squamous cell carcinoma (SCC) is a rare tumour of the ocular region and microscopic radical surgical is difficult. There are no single guidelines for therapeutic management and the role of radiation therapy is not clearly defined although conventionally photon or electron beams are used. Proton beam radiotherapy (PBRT) is a new option for a conservative approach and allows good sparing of the organs at risk. Materials and methods: After surgical resection, we collected 15 cases treated at our institution with PBRT. The dose delivered was between 48 and 60 Gy relative biological effectiveness (RBE), with fractions of 12–15 Gy RBE. Results: After an average period of 48 months, the patients achieved excellent disease control (overall survival and disease-free survival: 86·6%), with minimal acute and late toxicity. Findings: In this work, we present our experience on the use of PBRT technique in SCC treatment. A larger sample of patients is needed to draw conclusions about the impact of this treatment on disease recurrence and overall survival.

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The impact of tumour regression in locally advanced carcinoma cervix during external beam radiotherapy and the need for adaptive planning

10.1055/s-0039-1685287 ◽

2016 ◽

Keyword(s):

Ct Scan ◽

Locally Advanced ◽

Target Volume ◽

Ct Images ◽

Tumour Regression ◽

Target Coverage ◽

Carcinoma Cervix ◽

Advanced Carcinoma ◽

The Impact ◽

Planning Ct

Aim: To study the impact of tumour regression occurring during IMRT for locally advanced carcinoma cervix and study dose distribution to target volume and OARs and hence the need for any replanning. Materials and Methods: 40 patients undergoing IM-IGRT and weekly chemotherapy were included in the study. After 36 Gy, a second planning CT-scan was done and target volume and OARs were recontoured. First plan (non-adaptive) was compared with second plan (adaptive plan) to evaluate whether it would still offer sufficient target coverage to the CTV and spare the OARs after having delivered 36 Gy. Finally new plan was created based on CT-images to investigate whether creating a new treatment plan would optimize target coverage and critical organ sparing. To measure the response of the primary tumour and pathologic nodes to EBRT, the differences in the volumes of the primary GTV and nodal GTV between the pretreatment and intratreatment CT images was calculated. Second intratreatment IMRT plans was generated, using the delineations of the intratreatment CT images. The first IMRT plan (based on the first CT-scan or non adaptive plan) was compared with second IMRT plan (based on the second CT-scan or adaptive plan). Results: 35% patients had regression in GTV in the range of 4.1% to 5%, 20% in the range of 1.1%-2%, 15% in the range of 2.1%-3% and 20% in the range of 6%-15%. There was significant mean decrease in GTV of 4.63 cc (p=0.000). There was a significant decrease in CTV on repeat CT done after 36 Gy by 23.31 cc (p=0.000) and in PTV by 23.31 cc (p=0.000). There was a statistically significant increase in CTV D98, CTV D95, CTV D50 and CTV D2 in repeat planning CT done after 36 Gy. There was no significant alteration in OARs doses. Conclusion: Despite tumour regression and increased target coverage in locally advanced carcinoma cervix after a delivery of 36 Gy there was no sparing of OARs. Primary advantage of adaptive RT seems to be in greater target coverage with non-significant normal tissue sparing.

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Impact of Pancreatic Resection on Survival in Locally Advanced Resectable Gastric Cancer

Cancers ◽

10.3390/cancers13061289 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1289

Author(s):

Shih-Chun Chang ◽

Chi-Ming Tang ◽

Puo-Hsien Le ◽

Chia-Jung Kuo ◽

Tsung-Hsing Chen ◽

...

Keyword(s):

Lymph Node ◽

Pancreatic Resection ◽

Locally Advanced ◽

Survival Rates ◽

Disease Free Survival ◽

Complication Rates ◽

Lymph Node Yield ◽

Whipple’S Operation ◽

Whipple's Operation ◽

The Impact

Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR); group 2 (G2), pT4b with PR; group 3 (G3), positive duodenal margins without Whipple’s operation; and group 4 (G4), cT4b with Whipple’s operation. Demographics, clinicopathological features, and outcomes were compared between G1 and G2 and G3 and G4. G2 patients were more likely to have perineural invasion than G1 patients (80.6% vs. 50%, p < 0.001). G4 patients had higher lymph node yield (40.8 vs. 31.3, p = 0.002), lower nodal status (p = 0.029), lower lymph node ratios (0.20 vs. 0.48, p < 0.0001) and higher complication rates (45.2% vs. 26.3%, p = 0.047) than G3 patients. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly longer in G1 than in G2 (28.1% vs. 9.3%, p = 0.003; 32% vs. 13%, p = 0.004, respectively). The 5-year survival rates did not differ between G4 and G3 (DFS: 14% vs. 14.4%, p = 0.384; OS: 12.6% vs. 16.4%, p = 0.321, respectively). In conclusion, patients with T4b lesion who underwent PR had poorer survival than those who underwent resection of other adjacent organs. Further Whipple’s operation did not improve survival in pT3–pT4 GC with positive duodenal margins.

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Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01796-4 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Paulo L. Pfitzinger ◽

Laura Fangmann ◽

Kun Wang ◽

Elke Demir ◽

Engin Gürlevik ◽

...

Keyword(s):

Pancreatic Cancer ◽

Mouse Model ◽

Tumor Stage ◽

Ache Inhibitors ◽

Impact On Survival ◽

The Impact ◽

Ache Expression ◽

Cholinergic Activation

Abstract Background Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. Methods We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/−physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. Results We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. Conclusion For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.

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Patients With Invasive Breast Cancer Who Refuse Treatment: An Analysis of Associated Factors and Impact on Survival

The American Surgeon ◽

10.1177/00031348211024170 ◽

2021 ◽

pp. 000313482110241

Author(s):

Jackelyn J. Moya ◽

Ashkan Moazzez ◽

Junko J. Ozao-Choy ◽

Christine Dauphine

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Invasive Breast Cancer ◽

Risk Groups ◽

Breast Cancer Treatment ◽

Study Cohort ◽

National Cancer Database ◽

Optimal Outcomes ◽

Impact On Survival ◽

The Impact

Background Completion of surgical resection and adjuvant/neoadjuvant treatments (chemotherapy, radiation, and endocrine therapy) is necessary to achieve optimal outcomes in invasive breast cancer. The objective of this study was to determine the characteristics of patients refusing treatment and to analyze the impact of refusal on survival. Study Design A retrospective cohort study of invasive breast cancer cases diagnosed 2004-2016 was performed utilizing the National Cancer Database. Results Of 2 058 568 cases comprising the study cohort, .6% refused recommended surgery, 14.1% refused chemotherapy, 5.5% refused radiation, and 6.3% refused endocrine therapy. Patients refusing therapy were older and more likely uninsured; they did not live farther from the treating hospital. Racial disparities were also associated with refusal. Surgery refusal had the highest hazard ratio for mortality (2.7; 95% CI: 2.5-3.0, P < .001) compared to chemotherapy (1.3; 95% CI: 1.3-1.4, P < .001), radiation (1.8; 95% CI: 1.7-1.9, P < .001), and endocrine therapy (1.5; 95% CI: 1.4-1.6, P < .001) independent of race, insurance, receptor status, and stage. Conclusion This study demonstrates significant associations with refusal of breast cancer treatment and quantifies the impact on mortality, which may help to identify at-risk groups for whom interventions could prevent increases in mortality associated with declining treatment.

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