scholarly journals High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases

Author(s):  
Viola Freitag ◽  
Sebastian Lettmaier ◽  
Sabine Semrau ◽  
Markus Hecht ◽  
Konstantinos Mantsopoulos ◽  
...  

Abstract Purpose Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy. Methods Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan–Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis). Results The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards. Conclusion With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.

Head & Neck ◽  
2016 ◽  
Vol 38 (S1) ◽  
pp. E2041-E2048 ◽  
Author(s):  
Marlen Haderlein ◽  
Claudia Scherl ◽  
Sabine Semrau ◽  
Sebastian Lettmaier ◽  
Wolfgang Uter ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


1999 ◽  
Vol 113 (7) ◽  
pp. 686-688 ◽  
Author(s):  
R. P. Hogg ◽  
C. Ayshford ◽  
J. C. Watkinson

AbstractIt is well recognized that, in general, chronic inflammation can predispose to malignant change. There is however, to our knowledge, no previously reported association between chronic obstructive sialadenitis and salivary gland epithelial malignancy. We describe here the first reported example in the English literature of a salivary duct carcinoma arising in a parotid gland with a long history of chronic obstructive sialadenitis. It is possible that a causal relationship exists between the two conditions. If this were the case then non-surgically treated chronic obstructive sialadenitis patients may well warrent careful clinical follow-up.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii86-iii86
Author(s):  
T Reynaud ◽  
A Bertaut ◽  
W Farah ◽  
D Thibouw ◽  
G Crehange ◽  
...  

Abstract BACKGROUND The standard of care for patients with recurrent glioblastoma or grade III glioma has not yet been clearly defined and many approaches are available for salvage strategies. These include surgery, re-irradiation or systemic agents. For the treatment of High-Grade (HGG) recurrence by radiation therapy, Hypofractionated Stereotactic Radiotherapy (HFSRT) is an interesting approach because it is minimally invasive, ambulatory, short-lasting and well tolerated. The aim of this study was to evaluate the efficacy of and safety to HFSRT as alvage treatment for patients suffering from HGG relapse in our cancer center and to compare these results with the literature. MATERIAL AND METHODS Between March 2012 and March 2017, 32 consecutive patients (12 women, 20 men) treated in a single-center were retrospectively included included in this study.Grade III gliomas were diagnosed in 14 patients and grade IV in 18 patients. Thirty-four lesions were treated with HFSRT on LINAC. HFSRT delivered a dose of 30 Gy in six fractions of 5Gy (27 Gy in three fractions for one patient) with two or three fractions per week. The treatment plans were normalized to 100% at the isocenter, and prescribed to the 80 % isodose line. Clinical outcomes and prognostic factors were analyzed. RESULTS HFSRT characteristics: The median tumor volume was of 6.1 (0.1–42.2) cm3 and the median PTV was 15 (0.6–67.5) cm3. The median maximum dose, median minimum dose and median mean dose were 38.7 (32.7–42.0) Gy, 29.1 (14.0–32.4) Gy and 35.1 (31.5–37.5) Gy, respectively. Median follow-up was 20.9 months. Median overall survival (OS) following HFSRT was 15.6 months (Median OS for patients patients with GBM and grade III glioma were 8.2 and 19.5 months, respectively; p=0.0496). Progression-free survival (PFS) was 3.7 months (Median PFS for patients with GBM and grade III glioma were 3.6 and 4.5months, respectively; p=0.2424). In multivariate analysis, tumor grade III (p=0.0027), an ECOG status <2 at the time of reirradiation (p=0.0023) and a mean dose >35 Gy (p=0.0055) significantly improved OS. A maximum reirradiation dose above 38 Gy (p=0.0179) was significantly associated with longer PFS. Treatment was well tolerated, no acute toxicity > grade 2 was observed. During the follow-up, ten patients (31.25%) had suspected radionecrosis. In six patients, this suspicion corresponded to tumor progression. For the other patients, radionecrosis was suggested on multi-modal MRI. CONCLUSION HFSRT appears to be a feasible and effective salvage treatment option for recurrent high-grade gliomas, with OS of 15.6 months. Prognostic factors associated with longer OS were a good general state of health and grade III glioma. Dosimetric data suggested that the dose gradient had an impact on tumor control and indicate that a study with dose-escalation is warranted. These results need to be confirmed in a prospective study with a greater number of patients.


2003 ◽  
Vol 14 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Steven D. Chang ◽  
Gordon T. Sakamoto

Object Hemangiopericytomas represent a small subset of meningeal tumors. Despite their relatively uncommon nature, they are aggressive tumors known for recurrence. Resection is the standard treatment in most, although regrowth and metastases are common even after resection. The authors evaluate the role of stereotactic radiosurgery in the treatment of recurrent hemangiopericytomas. Methods In a review of the Stanford radiosurgery patient database between 1989 and 2002, the authors found eight patients with recurrent hemangiopericytoma who underwent stereotactic radiosurgery. The mean age of this population was 45.1 years (range 24–67 years). All patients had been previously treated with resection, and five patients (63%) had undergone conventional radiotherapy. The mean radiosurgery dose to the tumor margin was 20.5 Gy (range 16–24 Gy). The mean clinical and radiographic follow-up period was 44 months (range 8–77 months). Of the eight tumors treated with radiosurgery, six decreased in size and two ultimately progressed. There were no radiosurgery-related complications. Conclusions Stereotactic radiosurgery of hemangiopericytomas can result in increased tumor control and should be considered as a treatment option for patients in whom the diagnosis has been established and in whom residual tumor is demonstrated postoperatively. Close clinical and radiographic follow-up evaluation is necessary in this patient population because of the high rate of local recurrence and distant metastases.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5356-5356
Author(s):  
Hugues de Lavallade ◽  
Reda Bouabdallah ◽  
Catherine Faucher ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
...  

Abstract This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT. Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years). In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR. We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16548-e16548
Author(s):  
H. Kiyohara ◽  
S. Kato ◽  
T. Ohno ◽  
Y. Ohkubo ◽  
T. Tamaki ◽  
...  

e16548 Background: Malignant melanoma of the female genital organs is a very rare tumor and resistant to conventional photon radiotherapy. We report six cases of female genital malignant melanoma those were well controlled locally by carbon ion radiotherapy (CIRT). Methods: Between November 2004 and October 2008, six patients with unresectable female genital malignant melanoma were treated with CIRT. Age of the patients ranged from 55 to 80 years (median; 69 years). Four patients had previously untreated locally invasive tumors and other two had locally recurrent tumors after surgery and adjuvant chemotherapy. The tumor located in the vagina (4 patients), both the cervix and the vagina (1 patient), or both the vagina and the vulva (1 patient). Two patients had inguinal lymph node metastasis and two had distant metastases at CIRT. All patients received a total dose of 57.6 gray equivalent (GyE) in 16 fractions over 4 weeks of CIRT. Three patients received chemotherapy using dacarbazine, ACNU, and vincristine after CIRT. Results: The follow-up durations after CIRT were from 9 to 20 months (median; 13 months). No patient developed severe acute toxicity during CIRT. No late toxicity of greater Grade 2 was experienced, while Grade 1 proctitis was observed in a patient. All tumors completely responded to CIRT. No patient developed in-field recurrence. The four patients without distant metastasis were alive with no evidence of disease for 9–20 months after CIRT. The two patients with distant metastases died from metastatic disease 13 and 18 months after CIRT, respectively. Conclusions: CIRT achieved favorable local tumor control without developing severe acute and late toxicity in the treatment of unresectable malignant melanoma of the female genital organs. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6086-6086 ◽  
Author(s):  
Samuel Rack ◽  
Yonghan Li ◽  
Craig McKay ◽  
Andrew Wallace ◽  
Robert Metcalf

6086 Background: For most patients with recurrent or metastatic salivary gland cancer (RM-SGC), there are no standard therapies. Many patients undergo genomic profiling to guide selection of targeted therapy. The MSK-IMPACT study applied a 468 gene next generation sequencing (NGS) panel, identifying actionable mutations in 34/114 patients (30%) with RM-SGC. Minimising cost will facilitate application within publically funded healthcare systems. We therefore sought to determine the utility of genomic profiling using a focused 24 gene targeted NGS panel to identify actionable mutations in RM-SGC with a sub-group analysis in adenoid cystic carcinoma (ACC) and non-ACC sub-types. Methods: From January 2017 to 2018, 125 patients with RM-SGC provided informed consent to an ethically approved study. Clinical and demographic characteristics were collected. DNA was extracted from FFPE samples and analysed using Qiagen GeneRead DNAseq Targeted Panel V2 in the Manchester Centre for Genomic Medicine Diagnostic Laboratory, an NHS clinically accredited lab. A custom bioinformatic pipeline was validated to detect single nucleotide variants and indels ( < 40bp) to 5% mutant allele frequency. Alterations were categorised following American College of Medical Genetics guidelines and Association for Molecular Pathology tiering. Results: DNA from 101 tumours (69 major, 32 minor salivary gland) was sequenced with 95% coverage at > 350x read depth over the target enrichment. 65 patients had adenoid cystic carcinoma (ACC) and 36 had non-ACC SGC. Median age was 55 years (range 18-80). 43 actionable alterations were identified in 33 patients within the following genes: TP53 (21%), PIK3CA (8%), ERBB2 (6%), PTEN (3%), BRAF (2%), EGFR (T790M) (1%), and AKT1 (1%). Targeted therapy was selected based on genomic findings in 12% of these patients. In ACC patients, actionable alterations were seen in 25% compared with 55% of non-ACC patients (9 adenocarcinoma, 5 salivary duct carcinoma, 3 carcinoma ex pleomorphic adenoma, 2 mucoepidermoid carcinoma and 1 myoepithelial carcinoma). Conclusions: This study identified actionable alterations in 33% of SGC patients using focused genomic profiling, demonstrating comparable utility to larger research panels. This focussed panel is being expanded to include emerging biomarkers such as NOTCH gene mutations, with NOTCH inhibitors currently in trials in ACC. Greater access to basket studies incorporating therapies matched to genomic alterations will maximise the clinical utility of this approach.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6529-6529
Author(s):  
Wim van Boxtel ◽  
Maike Uijen ◽  
Chantal Driessen ◽  
Sjoert Pegge ◽  
Stefan M. Willems ◽  
...  

6529 A phase II study on the efficacy and toxicity of cabozantinib in recurrent/metastatic salivary gland cancer patients. Background: Because c-MET and VEGFR are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in recurrent/metastatic (R/M) SGC pts. Methods: A single center, single arm, phase II study was conducted. Immunohistochemical c-MET positive (H-score ≥10) R/M SGC pts were included in 3 cohorts: adenoid cystic carcinoma (ACC), salivary duct carcinoma (SDC), and other SGCs. Objective growth or complaints due to the disease were required before inclusion in the ACC and other SGC cohort. No prior systemic treatments were required. Pts started 60 mg cabozantinib tablets OD. Primary endpoint was the objective response rate (ORR). A Simon two-stage design was used. In case of ≥1 objective response in the first 9 pts/cohort, 8 additional pts would be included in the cohort. Results: In total 25 pts were included from Sep. 2018 until premature closure due to severe toxicity in Nov. 2019. Median age was 56 years (range 49-72), prior treatments included: primary tumor resection ( n=19), radiotherapy ≥50Gy ( n=24), systemic therapy ( n=10; adjuvant in 2 pts, palliative in 8 pts). Six pts had grade 3 ( n=4), grade 4 ( n=1), or grade 5 ( n=1) wound/fistula complications, occurring at a median of 7.2 mths on cabozantinib (range 2.1-12.8). This resulted in a severe wound complication rate of 32% in 19 pts on treatment for ≥2 mths. Remarkably, 4 out of 6 pts developed this complication in the area exposed to high-dose Rx; 2/4 had a pre-existing fistula in this area. Median interval between Rx and start of cabozantinib was 71.3 mths (range 10.6-94.7). Other grade ≥3 adverse events in >1 pt were: hypertension (5 pts), diarrhoea (2 pts) and dehydration (2 pts). Current median follow-up is 6.8 mths. The ORR was 6% (1/17 pts) in the ACC cohort, 20% (1/5 pts) in the SDC cohort, and 0% (0/3 pts) in other SGC pts; median PFS is 12.6 mths (95% CI 6.8 – 18.4 mths), 9.0 mths (insufficient events for 95% CI), and 6.9 mths (95% CI 0 – 15.2 mths), respectively. Median OS is not reached in any cohort. Conclusions: This phase II study on cabozantinib in R/M SGC pts demonstrated severe wound and fistula complications in 32% of pts on treatment for ≥2 mths, mostly (4/6 pts) within the radiotherapy field. Because of this toxicity the study was closed prematurely. Furthermore, cabozantinib showed minimal clinical activity in SGC pts. Research funding: Ipsen Pharmaceuticals Clinical trial information: NCT03729297 .


2014 ◽  
Vol 48 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Daniel E. Spratt ◽  
Lucas Resende Salgado ◽  
Nadeem Riaz ◽  
Michael G. Doran ◽  
Moses Tam ◽  
...  

Abstract Background. The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980’s reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution’s results of photon radiotherapy for unresectable salivary gland tumors. Patients and methods. From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. Results. With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient’s experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. Conclusions. Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.


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