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• 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. [ABSTRACT FROM AUTHOR]

In this contribution we give an overview of the mechanisms behind degradation of Cu(In,Ga)Se2-based modules. Based on the results from a detailed analysis of power losses in modules, prior to and after extended damp heat exposure, we discuss to what extent modules can be designed to achieve enhanced long-term performance. For conventional modules, we show that the stability can be improved by optimizing the interconnect and the front contact. Furthermore, we argue that gridded modules are better from a long-term performance point of view. A novel interconnect structure, specifically designed for long-term durability, is briefly discussed. [Copyright &y& Elsevier]

Deals with a study which examined alternatives to the conventional crystalline silicon photovoltaic (PV) technology for the mass production of low-cost PV technology. Discussion on thin film photovoltaics; Principles of the copper-indium-gallium-selenium thin film technology; Compound parabolic concentrators.

Abstract: We report karyotypic features of 106 short-term cultured oral squamous cell carcinomas (SCC), 51 new and 55 previously reported cases, with clonal chromosome aberrations. The major cytogenetic findings were as follows: simple karyotypic changes were present in 38 cases (36%) and 68 tumors (64%) displayed complex karyotypes. The most common numerical changes were +7, +8, +9, +16, +18, +20, and −4, −10, −13, −14, −18, −19, −21, −22, and −Y. Structural rearrangements frequently (43% of the breaks) affected the centromeric regions, resulting in the formation of isochromosomes and whole-arm translocations. Among the recurrent structural aberrations identified, the most common were i(1q), i(3q), i(5p), i(8q), del(16)(q22), and hsr. With the exception of chromosomal band 11q13, which was involved in 25 tumors, only centromeric or near-centromeric bands were commonly involved: 3p11∼q11 (59 cases), 8p11∼q11 (57), 1p11∼q11 (48), 13p11∼q11 (46), 5p11∼q11 (41), 14p11∼q11 (41), and 15p11∼q11 (37). Losses of genetic material dominated over gains. The most frequent imbalances included loss of 2q33∼qter, 3p, 4p, 6q, 8p, 10p, 11q, 13p, 14p, and 15p, and chromosomes 18, 21, 22, and Y, and gain of chromosomes 7 and 20, 8q, and 11q13. No major karyotypic differences could be discerned between the present series of oral SCC and a previously reported series of laryngeal SCC, indicating that common genetic pathways are involved in the initiation and progression of SCC irrespective of site of origin. [Copyright &y& Elsevier]

Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples. Two samples displayed both related and unrelated multiple clones, four samples showed only multiple unrelated clones, and the remaining 10 samples had only related subclones. Intersample heterogeneity was detected in all but one tumor. Five tumors showed both cytogenetically related and unrelated multiple clones, 11 were found to have only related subclones, and the remaining two tumors showed only unrelated clones. Clonal evolution could be assessed in 13 tumors. A comparison of chromosome imbalances in different subclones from these tumors suggests that partial or entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably later genetic events. One of the examined tumors contained two highly complex clones that were cytogenetically unrelated, indicating that this tumor had a multicellular origin. [Copyright &y& Elsevier]

• The prognosis for oral tongue cancer for young adults vs adults has been debated. • This is a population-based study of 1.146 patients treated with curative intent. • Excess mortality correlates with stage, tumor subsite, and lead times to treatment. • There was no difference in relative survival between the age groups. Increased incidence of squamous cell carcinoma (SCC) of the tongue has been reported in young adults (YA) in several countries since the 1980s and confirmed in later studies. The etiology is unclear, the prognosis has been debated, and conflicting results have been published. Some studies show better survival in young adults than in older patients, some worse, and others no difference. Most studies are based on selected series or include other sites in the oral cavity. The definition of "YA" is arbitrary and varies between studies. It is thus difficult to use in general conclusions. This work uses data from the population-based Swedish Head and Neck Cancer register (SweHNCR), which has > 98% coverage. SweHNCR data includes age, gender, TNM, treatment intention, treatment given, lead times, performance status, and to a lesser degree, smoking habits. The current Swedish population is around 10 million. We analyzed outcomes for 1416 patients diagnosed with SCC of the oral tongue from 2008 to 2017 using 18–39 years to define YA age because it is the range most commonly used. We found no significant difference in relative survival (a proxy for diagnosis-specific survival) between age groups of patients treated with curative intent for SCC of the oral tongue. The stage at time of diagnosis was equally distributed among the age groups. Excess mortality rate correlated mainly with stage, subsite of the tongue, performance status, and lead time to treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary Objectives Cetuximab is an epidermal growth factor receptor (EGFR)-targeting drug that has shown effects in head and neck squamous cell carcinoma (HNSCC). The effects are, however, small and have mainly been proven in a subset of patients, and the cost-effectiveness has been questioned. For this reason, we need to know more about the basic mechanisms controlling the effect of EGFR signalling on tumour growth. Materials and methods We investigated the effect of the EGFR ligand transforming growth factor alpha (TGF-α) and cetuximab, alone and in combination, on HNSCC cell lines, measuring proliferation and the activity of intracellular signalling pathways. Results In line with previous reports we found the majority of the cell lines to be growth-inhibited by TGF-α. Surprisingly, two of the cell lines, which were more thoroughly investigated, were either growth-inhibited or stimulated by both cetuximab and TGF-α, depending on the presence or absence of the other substance. We also present data indicating the existence of two different receptor activities emanating from the EGFR protein. Conclusion We therefore show that TGF-α can have both growth-stimulating and growth-inhibiting effects in the same cell line and that EGFR-targeting drugs can be similarly double-edged. The implication for such drugs is that the micro-environment within a tumour, and possibly within portions of a tumour, may influence the growth-inhibiting effect of the drug. There may also be important implications for our understanding of EGFR signalling and its influence on growth and development. [ABSTRACT FROM AUTHOR]

Summary: The role of chemotherapy (CHX) in squamous cell carcinoma of the head and neck (SCCHN) has been expanding. Although combination chemotherapy regimens regularly produce significantly high response rates, meta-analyses show little benefit regarding final outcome. One way to improve induction CHX is to improve drug combinations and schedules for CHX. Cisplatin (CDDP) is one of the most active drugs in the treatment of patients with SCCHN, and it is used in most combinations. Ifosfamide (IFO) is another agent that has shown activity in the treatment of patients with SCCHN. A poorly differentiated squamous cell carcinoma xenografted to nude mice was used. CDDP (2.5mg/kg) and IFO (100mg/kg) as single bolus doses induced significant retardation of tumour growth. Single drug administration was compared with CDDP given before IFO and IFO given before CDDP. Mean specific growth delay (SGD) for untreated controls was 0. For CDDP as single drug it was 1.50, for IFO as single drug it was 0.79, for CDDP given 4h before IFO it was 1.79, and for IFO given 4h before CDDP it was 2.90. Maximum toxicity, calculated as change in median weight at day 7, was less than 10%. The efficacy and toxicity of CDDP and IFO is schedule-dependent, with IFO given before CDDP being more effective than CDDP given before IFO. This is in contrast to most schedules used clinically. The toxicities were comparable. The number of combinations of drugs with respect to order and time interval is of a magnitude that would not be possible to test clinically. In the pursuit of more efficient combinations, the importance of order and schedule of drugs and also the potential of xenografted SSCHN are underestimated. [ABSTRACT FROM AUTHOR]

Abstract: Cytogenetic analysis was performed on primary tumors, and paired recurrent or metastatic lesions, in 14 patients with head and neck squamous cell carcinomas (HNSCC), in order to identify chromosomal aberrations associated with tumor initiation and progression. Abnormal karyotypes were found in 12 of the 14 patients, with distinctive karyotypic similarities shown in all informative pairs. For individual patients, the degree of karyotypic complexity was similar for the primaries and paired recurrent or metastatic lesions. All 22 samples with clonal chromosomal aberrations displayed complex karyotypes with multiple numerical and unbalanced structural rearrangements, resulting in extensive genomic imbalances. The pathway of clonal evolution could be traced in a few patients, supporting the notion that some aberrations or imbalances, particularly partial or entire loss of 3p, i(8q), and homogeneously staining regions commonly mapping to 11q13, were early genetic events in the initiation of HNSCC. [Copyright &y& Elsevier]

Amplification of CCND1 (cyclin D1 gene) in squamous cell carcinoma of the head and neck (SCCHN) is correlated to poor prognosis. The purpose of this study was to investigate whether CCND1 amplification is related to different subsites and also to DNA ploidy status and S-phase fraction (SPF). Biopsies from 67 patients with SCCHN were analysed for CCND1 amplification by fluorescence in situ hybridisation (FISH) and for ploidy status and SPF by flow cytometry (FCM).Twenty-one of 67 tumours (31%) showed CCND1 amplification and the frequencies differed significantly between different subsites (p=0.01). Tumours from hypopharynx, larynx and oropharynx showed higher rates of amplification as compared to tumours from oral cavity and epipharynx. CCND1 amplification was also associated to DNA non-diploidy and high SPF (p=0.002 and p=0.002, respectively). In conclusion, the rate of CCND1 amplification differed between different subsites in SCCHN and was also associated to a more aggressive tumour phenotype, as defined by DNA non-diploidy and high SPF. [Copyright &y& Elsevier]

Two lesions, actinic keratosis (AK) and squamous cell carcinoma in situ (CIS), are believed to be precursors of squamous cell carcinoma (SCC) of the skin. These lesions can serve as an excellent model system for studying genetic changes associated with the inception of skin SCC. In the present study, five such lesions of the skin, three AKs and two AK+CIS, from three patients were short-term cultured and analyzed cytogenetically. One of the patients (case 3) had also an SCC in addition to three premalignant lesions. All lesions, but one, showed clonal karyotypic abnormalities. The recurrent changes identified were numerical, that is, +7 and +20. The structural rearrangements found in three AK were different, but it could be noted that the distal part of the long arm of chromosome 4 was involved in two AK and the SCC of case 3A. It was also interesting that chromosome 1 participated in structural rearrangements in three AK with band 1p31 being involved in two tumors. The karyotypic profile of these lesions is compared with that of skin SCC; it turns out that the general patterns are different in the sense that the SCC more often have complex karyotypes and display unbalanced aberrations involving the centromeric regions. Some karyotypic similarities between the SCC and their precursors are revealed. The fact that the structural rearrangements involving chromosomal band 3p13 and the centromeric region of chromosome 3 in AK are common features for many types of malignant tumors, including skin SCC, indicates that these changes are early genetic events associated with malignant transformation. [Copyright &y& Elsevier]