Abstract
Conclusion: This study shows a persistent trend of an increase in the incidence of carcinoma of the tongue into the twenty-first century for both sexes and all age groups except for young ...males. Objectives: During the last decades increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been reported. We previously showed an increased incidence in SCC of the tongue in Scandinavia in 1960-1994, most pronounced in patients aged 20-39 years. The aim of this study was to investigate whether the trend of increased incidence of tongue cancer continued into the twenty-first century in a population-based study in the Nordic countries. Methods: Data for all reported SCCs of the tongue and base of tongue in patients aged 20-79 years during 1960-2008 were extracted from the NORDCAN registry, based on the National Cancer registries in the Nordic countries. Data from Sweden, Norway, Finland, Denmark, and Iceland were analyzed. The age groups 20-39, 40-64, and 65-79 years were studied separately as well as male and female figures. Results: In all, 12 280 cases were reported, of which 673 were diagnosed in patients aged 20-39 years. The trend of an increase persisted after 1994 in both sexes and all three age groups except in young males.
The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with ...brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.
Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.
Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64-72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II-III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.
In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
Anaplastic thyroid cancer (ATC) is a highly malignant disease with a very short median survival time. Few studies have addressed the underlying somatic mutations, and the genomic landscape of ATC ...thus remains largely unknown. In the present study, we have ascertained copy number aberrations, gene fusions, gene expression patterns, and mutations in early-passage cells from ten newly established ATC cell lines using single nucleotide polymorphism (SNP) array analysis, RNA sequencing and whole exome sequencing. The ATC cell line genomes were highly complex and displayed signs of replicative stress and genomic instability, including massive aneuploidy and frequent breakpoints in the centromeric regions and in fragile sites. Loss of heterozygosity involving whole chromosomes was common, but there were no signs of previous near-haploidisation events or chromothripsis. A total of 21 fusion genes were detected, including six predicted in-frame fusions; none were recurrent. Global gene expression analysis showed 661 genes to be differentially expressed between ATC and papillary thyroid cancer cell lines, with pathway enrichment analyses showing downregulation of
signalling as well as cell adhesion molecules in ATC. Besides previously known driver events, such as mutations in
,
,
and the
promoter, we identified
and
as putative novel target genes in ATC, based on deletions in six and four cell lines, respectively; the latter gene also carried a somatic mutation in one cell line. Taken together, our data provide novel insights into the tumourigenesis of ATC and may be used to identify new therapeutic targets.
•Randomised controlled trial on squamous carcinoma of the oral cavity.•Preoperative radical radiotherapy with accelerated fractionation vs. postoperative conventionally fractionated (± chemo-) ...radiotherapy.•Similar outcome regarding tumour control but more acute side-effects with preoperative accelerated radiotherapy.
An earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.
Patients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.
250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.
Toxicity was more pronounced in preoperative AF.
This study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.
Purpose: To investigate the effect of
191Pt-cisplatin
in vivo in terms of the antitumor effect and general toxicity on tumor-bearing nude mice.
Methods and Materials: Tumor-bearing (human squamous ...cell carcinoma, ÅB) nude mice were divided into four groups and given, i.p., physiological saline (controls), cisplatin,
191Pt-cisplatin (80 MBq/mg), or
191Pt-cisplatin (160 MBq/mg), respectively. Mortality and weight were used as parameters for monitoring general toxic effect, while specific growth delay (SGD) and the area under the logarithm of the relative tumor size curve (AUC-logRTS) were used to evaluate the antitumor effect of the treatments.
Results: Both SGD and AUC-log(RTS) values showed that
191Pt-cisplatin was significantly (
P < 0.05) more effective in retarding tumor growth than nonradioactive cisplatin. No differences in mortality between the different groups could be observed and no significant differences in weight change between the mice treated with cisplatin or
191Pt-cisplatin could be seen.
Conclusion:
191Pt-cisplatin is a more effective drug than nonradioactive cisplatin in retarding tumor growth on nude mice without adding systemic toxic effects. We believe that radioactive cisplatin may prove to be an alternative to conventional cisplatin; however, the possible toxic effects on organs at risk have to be thoroughly investigated.
Purpose
Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early ...rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes.
Methods
Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1–6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated.
Results
The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line.
Conclusion
A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity.
Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate ...that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3.
There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3.
Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery.This further suggests that the decreased survival during erythropoietin treatment might be due to inhibition of apoptosis.
Abstract Background and purpose This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal ...cancers. Material and methods Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1–2, N0 glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms ( p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) ( p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16− tumours. Conclusion This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.
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