Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor

Contains fulltext : 69595.pdf (publisher's version ) (Closed access)PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy

Background matching in the brown shrimp Crangon crangon : adaptive camouflage and behavioural-plasticity

A combination of burrowing behaviour and very efficient background matching makes the brown shrimp Crangon crangon almost invisible to potential predators and preys. This raises questions on how shrimp succeed in concealing themselves in the heterogeneous and dynamic estuarine habitats they inhabit and what type of environmental variables and behavioural factors affect their colour change abilities. Using a series of behavioural experiments, we show that the brown shrimp is capable of repeated fast colour adaptations (20% change in dark pigment cover within one hour) and that its background matching ability is mainly influenced by illumination and sediment colour. Novel insights are provided on the occurrence of non-adaptive (possibly stress) responses to background changes after long-time exposure to a constant background colour or during unfavourable conditions for burying. Shrimp showed high levels of intra- and inter-individual variation, demonstrating a complex balance between behavioural-plasticity and environmental adaptation. As such, the study of crustacean colour changes represents a valuable opportunity to investigate colour adaptations in dynamic habitats and can help us to identify the mayor environmental and behavioural factors influencing the evolution of animal background matching

Prognostic factors for long term results of the treatment of patients with malignant submandibular gland tumors

BACKGROUND: Concerning malignant submandibular gland tumors, a rare disease entity, there are few recent reports of long term treatment results and of prognostic factors modifying these results. METHODS: The clinical data of 43 patients with malignant submandibular gland tumors who were treated at the Netherlands Cancer Institute between 1973 and 1994 were reviewed to evaluate treatment results and to control described prognostic factors. The median follow-up for patients alive at the end of follow-up was 143 months. Only univariate analyses were performed. RESULTS: The crude 5- and 10-year survival rates were 50% and 36%, respectively; the 5- and 10-year disease specific survival (DSS) rates were 61% and 51%, respectively; and the 5- and 10-year recurrence free percentages were 57% and 52%, respectively. Factors predicting crude survival were age at diagnosis (P = 0.0006), International Union Against Cancer/American Joint Committee on Cancer (UICC/ AJCC) TNM classification and its regrouping into tumor stage (P = 0.001), and clinical skin invasion (P = 0.005). In surgically treated patients, soft tissue invasion (P = 0.005), metastatic lymph nodes (P = 0.006), and perineural growth (P = 0.01) were prognostic for survival. Factors predicting DSS were the UICC/AJCC TNM classification and regrouping into tumor stage (P = 0.002). In surgical patients, perineural growth (P = 0.0008) conferred a lower DSS. Factors predicting tumor recurrence were the UICC/AJCC TNM classification and its regrouping into tumor stage (P = 0.009). In surgical patients, perineural growth (P = 0.003) predicts tumor recurrence. CONCLUSIONS: Of patients with submandibular gland carcinoma treated according to a stable treatment protocol in a European tertiary referral center, 52% were tumor free 10 years later. Patients exhibiting the described adverse prognostic factors are likely to benefit from added radiotherapy.status: publishe

The development of a prognostic score for patients with parotid carcinoma

BACKGROUND: Understanding of prognostic factors in parotid carcinoma has grown considerably. In particular, clinical tumor staging and histologic classification have been found to be prognostically important. Univariate and multivariate analyses have indicated that other variables, such as age, pain, skin invasion, and facial nerve impairment, are important predictors as well. In an actual patient, some of these factors are present and others are absent. However, a clinical tool incorporating this information, resulting in an individualized prognosis based on the combined effects of present adverse prognostic factors, has never been devised. METHODS: Of a cohort of 168 patients, 151 were evaluated to assess the prognostic value of clinical and pathologic factors in a multivariate proportional hazards analysis. Follow-up ranged from 1 to 278 months (median, 37 months). The end point was tumor recurrence. Identified prognostic factors and their hazard ratios were combined into prognostic scores. RESULTS: Clinical T classification, clinical N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins acted as major factors predicting recurrence. A prognostic score (PS), generated by the weighted combination of the factors present in the individual patient, placed the patient in one of four subgroups with markedly different prognoses. In the subgroups based on the preoperative prognostic score, 5-year recurrence free percentages ranged from 92% (in the group PS1=1) to 23% (in PS1=4). In the subgroups based on the postoperative prognostic score, which took into account the histologic details of the resected specimen, 5-year recurrence free percentages ranged from 95% (in the group PS2=1) to 42% (in PS2=4). CONCLUSIONS: The proposed subgrouping, which is based on the combined effects of key prognostic preoperative and postoperative factors, provides a practical prognostic grouping system for the clinician treating patients with parotid carcinoma.status: publishe

Voice quality and surgical detail in post-laryngectomy tracheoesophageal speakers

The objective of this study is to assess surgical parameters correlating with voice quality after total laryngectomy (TL) by relating voice and speech outcomes of TL speakers to surgical details. Seventy-six tracheoesophageal patients' voice recordings of running speech and sustained vowel were assessed in terms of voice characteristics. Measurements were related to data retrieved from surgical reports and patient records. In standard TL (sTL), harmonics-to-noise ratio was more favorable after primary TL + postoperative RT than after salvage TL. Pause/breathing time increased when RT preceded TL, after extensive base of tongue resection, and after neck dissections. Fundamental frequency (f0) measures were better after neurectomy. Females showed higher minimum f0 and higher second formants. While voice quality differed widely after sTL, gastric pull-ups and non-circumferential pharyngeal reconstructions using (myo-)cutaneous flaps scored worst in voice and speech measures and the two tubed free flaps best. Formant/resonance measures in/a/indicated differences in pharyngeal lumen properties and cranio-caudal place of the neoglottic bar between pharyngeal reconstructions, and indicate that narrower pharynges and/or more superiorly located neoglottic bars bring with them favorable voice quality. Ranges in functional outcome after TL in the present data, and the effects of treatment and surgical variables such as radiotherapy, neurectomy, neck dissection, and differences between partial or circumferential reconstructions on different aspects of voice and speech underline the importance of these variables for voice quality. Using running speech, next to sustained/a/, renders more reliable results. More balanced data, and better detail in surgical reporting will improve our knowledge on voice quality after TL