Impact of initial tumor volume on radiotherapy outcome in patients with T2 glottic cancer.

BACKGROUND: The aim of this study was to quantify the impact of initial tumor volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer. MATERIALS AND METHODS: Initial TV was calculated for 115 consecutive patients with T2 glottic cancer who had been treated with definitive RT alone at a single institution. RESULTS: The results showed strong correlations of TV with 3-year local tumor control (LTC) and disease-free survival (DFS). For TV ≤ 0.7 cm(3), 3-year LTC was 83%; for TV 0.7-3.6 cm(3) this was 70% and for TV 3.6-17 cm(3) 44%. Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a TV of around 5 cm(3) (2-2.5 cm in diameter with 10(10) cancer cells) need an extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of 0.5 cm(3) (~1 cm in diameter with 10(9) cancer cells). CONCLUSION: Although classification of tumors according to TV cannot replace TNM staging in daily practice, it could represent a valuable numerical supplement for planning the optimal dose fractionation scheme for individual patients.

Prognostic role of tumor volume for radiotherapy outcome in patient with T2 laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor volume (TV) is recognized as a prognostic factor of treatment outcome for head and neck tumors but is not routinely included in the treatment decision-making process. The purpose of the study was to define its prognostic role for patients with T2 laryngeal cancer. MATERIAL AND METHODS: TV of 160 patients who underwent RT between 2002 and 2006 for T2 laryngeal squamous cell carcinoma were reviewed. The tumor was located in the glottis and epiglottis in 82 (51%) and 78 (49%) patients, respectively. TV was manually contoured on pretreatment, planning, contrast-enhanced CT scans and the volumetric measurement (cm3) was calculated by the volume algorithm. RESULTS: The median TV value was 2.01 cm3 (range 0.15-21.68 cm3). The median TV was significantly lower in patients with glottic tumors (p<0.0001), N0 (p<0.001), or well histopatologically differentiated tumors (p=0.01). A significant correlation between TV, hemoglobin concentration (p<0.01), and total dose (TD; p<0.001) was observed. On univariate analyses, TV influenced local control (LC; p=0.02) and overall survival (OS, p<0.001). On multivariate analysis, both age (HR 1.038, p=0.03) and TV (HR=1.075, p=0.01) remained significantly related to LC and OS (age: HR 1.038, p=0.005; TV: HR 1.097, p=0.0001). CONCLUSION: Large TV worsen prognosis of patients with T2 laryngeal cancer. A large TV is more common for supraglottic, poorly differentiated tumors and may suggest higher risk of nodal spread. The routine estimation of TV prior to therapy may be essential in order to select the best treatment option for patients with T2 laryngeal cancer.

Ewing's sarcoma of the larynx. Effective treatment with organ preservation.

Extraskeletal Ewing's sarcoma arising in the head and neck region is an extremely rare malignant neoplasm. We describe the unusual case of a tumor originating in the larynx of a 68-year-old male with hoarseness and occasional aphonia. We report successful treatment with sequential chemo- and radiotherapy. Complete regression and larynx preservation with voice function recovery was achieved. To our knowledge, this is the first report of this type of tumor in the larynx with cartilage invasion that documents the effectiveness of radiotherapy as an alternative to surgical management. At present, after 30 months of follow-up, the patient is free of tumor relapse and in very good condition.

Acute mucosal reactions in patients with head and neck cancer. Three patterns of mucositis observed during radiotherapy.

PURPOSE: To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. MATERIALS AND METHODS: Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. RESULTS: A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase-plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase-plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. CONCLUSION: The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction--visible as a plateau phase on the course curve--is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.

Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma.

BACKGROUND: The precise analysis of tumour markers in blood such as circulating cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring of patients after initial therapy. Although high levels of total cfDNA in plasma of cancer patients are consistently demonstrated, a low sensitivity of DNA alterations is reported. OBJECTIVE: The major question regards the recovery of tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of human papillomavirus (HPV16). METHODS: TaqMan technology was used for detection of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. RESULTS: Comparison of four different column-based commercial kits shows that the cfDNA purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity of detection of KRAS mutation and HPV16. The optimized method was used to follow the reduction in cancer-specific cfDNA after therapy. We found that large volume extractions with low volume of DNA eluate enabled trace amounts of tumour-specific cfDNA from cancer patients to be effectively identified. CONCLUSIONS: Data presented in this study facilitate detection of tumour-specific cfDNA and improve standards needed for the implementation of cfDNA technology into routine clinical practice.

Acute mucosal radiation reactions in patients with head and neck cancer. Patterns of mucosal healing on the basis of daily examinations.

PURPOSE: The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. MATERIALS AND METHODS: In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. RESULTS: Duration of healing after the end of radiotherapy ranged widely (12-70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. CONCLUSION: The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients.

Efficacy and toxicity of MDR versus HDR brachytherapy for primary vaginal cancer.

The retrospective analysis includes a group of 50 patients with primary, invasive vaginal cancer treated with brachytherapy in the period of 1982-1993. Over 80% cases were squamous cell carcinoma. There were 14 patients in stage I according to FIGO classification and 20%, 36%, and 16% of patients in stage II, III and IV, respectively. Twenty one patients (42%) received MDR brachytherapy using Cs137 source, the remaining 29 (58%) were treated with HDR using Co60 or Ir192 sources. Among 50 patients 31 (62%) received also external beam irradiation. An overall 5-year actuarial disease-free survival was 40%, and it was 78.6% (11/14), 40% (4/10), 27.8% (5/18), 0% (0/8) for stage I, II, III and IV, respectively. For MDR or HDR5-year disease-free survival was 38% and 41%, respectively. No influence of dose rate on survival has been found (p=0.7). Local failure occurred in 20 patients (40%). Recurrences appeared in 10 patients (20%). Late complications rate was 0% and 17% for MDR and HDR, respectively. Effectiveness of brachytherapy MDR and HDR was similar, whereas serious late complications developed more often after HDR brachytherapy.

Estimation of speech embedded in a reverberant and noisy environment by independent component analysis and wavelets.

In this paper, we develop a system for enhancement of the speech signal with highest energy from a linear convolutive mixture of n statistically independent sound sources recorded by m microphones, where m

Influence of previous treatment on palliative effect of HDR brachytherapy in advanced esophageal cancer.

General effectiveness and influence of previous treatment on value of palliative HDR brachytherapy were assessed in 35 patients with advanced esophageal cancer treated from 1992 till 1997 with brachytherapy HDR (BT). Twelve of them were treated only with BT, II received previously chemoradiotherapy (CHTT), 12 teleradiotherapy (TT). BT appeared to be effective method of palliation. No significant differences in effectiveness of BT in analyzed groups were observed. Sever complications were observed in 9 cases (26%), and that in patients treated previously. Brachytherapy seems to be efficient after previous treatment, however, in this case, the risk of complications increases.

Neoplastic lesions of the human liver in relation to the activity of the cytochrome P-450 dependent monooxygenase system.

We studied the activity of Mixed function oxidase (MFO) in human livers affected by cancer. We determined the content of cytochrome P-450 and b5, as well as the activity of their corresponding reductases, according to generally accepted methods. Liver fragments corresponding with a) healthy tissue, b) tissue at the cancer border and, c) cancerous tissue were collected during surgery from patients with liver cancer. We noted that the developing liver cancer decreased the level of cytochrome P-450, even by a magnitude order. The activity of its corresponding reductase was higher in cancerous than in healthy tissues. Cytochrome b5 behaved in an analogous manner, although the decrease in its content was less significant. NADH-cytochrome b5 reductase activity changes were insignificant.

[The effectiveness of radiotherapy and the prognostic value of Hb level for patients with early glottic cancer (T1N0, T2N0)]. / Ocena skutecznosci radioterapii i wartosci prognostycznej poziomu hemoglobiny u chorych na raka glosni we wczesnym stopniu zaawansowania (T1N0, T2N0).

Effectiveness of radiotherapy as a sole treatment modality was analysed in a group of 225 patients with glottic cancer in stage T1 (153 patients) or T2 (72 patients) without metastases in regional neck lymph nodes. All patients were irradiated with gamma 60Co or 10 MeV photons 5 times per week conventional treatment with the dose of 2.0-2.5 Gy per fraction. The total dose was in the range of 60-70 Gy given in overall treatment time of 30-61 days. 3-year local control rate was 88% for T1 patients and 54% for T2. In group T1 total dose of 65-70 Gy correlated with a high, 94-100%, local rate whereas in group T2 for the same range of total dose, extension of overall treatment time beyond 45 days caused significant decrease in local tumour control of about 3% for each one day of treatment protraction. Moreover, the Hb level was found to be a significant prognostic factor and its value below 12 g/dl correlated with remarkably lower local control of glottic cancer of about 30% comparing with patients with Hb level above 12 g/dl.