Radiotherapy For Squamous Cell Carcinoma Research Articles

140 oral The DAHANCA 6 & 7 trial of 5 versus 6 fractions per week of conventional radiotherapy of squamous cell carcinoma (SCC) of the head and neck. A randomized study with 1485 patients

140 oral The DAHANCA 6 & 7 trial of 5 versus 6 fractions per week of conventional radiotherapy of squamous cell carcinoma (SCC) of the head and neck. A randomized study with 1485 patients

Radiation therapy alone or combined surgery and radiation therapy in squamous-cell carcinoma of the penis?

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35–76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent ( n=18) of the patients underwent surgery: partial penectomy with ( n=4) or without ( n=12) lymph node dissection, or total penectomy with ( n=1) or without ( n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy ( n=14). The median follow-up period was 70 months (range 20–331 months). In a median period of 12 months (range 5–139 months), 63% ( n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy ±postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy ( P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41–73%) and 38% (95% CI, 21–55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41–73%) and 48% (95% CI, 32–64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22–50%) and 18% (95% CI, 2–34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy ±salvage surgery, with 39% having organ preservation.

Altered fractionation in definitive irradiation of squamous cell carcinoma of the head and neck.

The likelihood of local control after radiation therapy may be improved by increasing total dose or decreasing overall time. The probability of late complications increases with dose per fraction. Altered fractionation techniques usually employ two or more fractions per day using a dose per fraction that is similar or less than that employed in conventional fractionation. Altered fractionation may be broadly classified as hyperfractionation or accelerated fractionation. Data suggest that altered fractionation schedules may improve local control (and to a lesser extent, survival) compared with conventional irradiation.

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2/24 h × 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2/24 h × 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123.

Relationship between tumour cell in vitro radiosensitivity and clinical outcome after curative radiotherapy for squamous cell carcinoma of the head and neck

Background and purpose: Clinically, it is recognized that individual tumours respond differently to radiation treatment. Variation in tumour cell radiosensitivity is believed to be an important underlying factor. In the current study, cellular in vitro radiosensitivity was estimated as the fraction of surviving cells after a radiation dose of 2 Gy (SF 2) and related to clinical outcome after curative radiotherapy. Patients and methods: Thirty-eight patients with squamous cell carcinoma of the head and neck were treated with curative radiotherapy alone. Pre-treatment biopsies were disaggregated to form a single-cell suspension and cells were cultured in the modified Courtenay–Mills soft agar clonogenic assay. Directly from this assay and with no respect to cell type, overall SF 2 was assessed. By collecting the obtained colonies on a preparation slide using a colony-filter technique, and with immunocytochemical staining, it was possible to measure the surviving fraction of tumour cells selectively as tumour cell SF 2. Results: Experimentally, a broad inter-tumour variation was found for both tumour cell SF 2 and overall SF 2. Using weighted linear regression, it was demonstrated that tumour cell SF 2 and overall SF 2 were two independent measures of tumour radiosensitivity. In general, the measures of tumour radiosensitivity were independent of patient sex and age, T- and N-category, disease stage, tumour size and plating efficiency. Among the 38 patients grouped in loco-regional failures and patients with loco-regional control, respectively, sex, age, total radiation dose, overall treatment time and tumour grade were equally distributed. Advanced stage, lymph node involvement and tumour size correlated statistically significantly with poor loco-regional control. Neither tumour cell SF 2, overall SF 2, nor plating efficiency predicted loco-regional tumour control probability. In a multivariate analysis with respect to the risk of loco-regional tumour failure, only disease stage yielded independent prognostic significance. This significance suggests that this patient sample was representative for the patient population with head and neck cancer. Conclusion: In 38 patients with squamous cell carcinoma of the head and neck, the estimated tumour radiosensitivities were not statistically related to clinical outcome after curative radiotherapy alone.

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival.

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.

An analysis of the prognostic significance of p53 status for squamous cell carcinoma of the oral cavity treated by radiotherapy.

The status of the p53 gene in biopsy specimens was analyzed to determine whether it is predictive of the outcome of radiotherapy of squamous cell carcinomas of the oral cavity. Biopsy materials were obtained from 45 patients, and the p53 status of each patient was determined using a single-strand conformation polymorphism analysis. Fourteen of the patients were treated with radiation therapy alone; the other 31 patients underwent radiotherapy in combination with surgery or chemotherapy. Twenty-seven patients had tumors with wild-type p53 and 18 patients had a tumor with mutant p53. The initial tumor response was not significantly different between these two groups. Kaplan-Meier survival plots (log-rank test) showed that the probability of survival was not significantly different between two groups although the patients with mutant p53 had a tendency for longer survival (P = 0.2941). However, among the patients with stage III/IV tumors (n = 24), those with a wild-type p53 status tended to have longer survivals.

102Local control after low dose rate endocavitary brachytherapy and external irradiation in squamous cell carcinoma of the nasal vestibule

102Local control after low dose rate endocavitary brachytherapy and external irradiation in squamous cell carcinoma of the nasal vestibule

Adjuvant Radiotherapy for Squamous Cell Carcinoma of the Tongue Base: Improved Local-Regional Disease Control Compared with Surgery Alone

Purpose: The purpose of this retrospective study is to present the results of postoperative adjuvant radiotherapy after primary surgery for squamous cell carcinoma of the tongue base and to compare these results to those obtained with surgery alone. Methods: Between 1974 and 1993, continuous-course postoperative radiotherapy was delivered to 24 patients (Adjuvant Radiotherapy Group). Results were compared to those from a group of 55 patients treated with surgery alone (Surgery Group). Results: Characteristics of the two groups were similar, except that a larger proportion of patients in the Adjuvant Radiotherapy Group had higher pathologic TNM stages. Ipsilateral neck control (87% vs. 68%, p = 0.04), contralateral neck control (100% vs. 76%, p = 0.002), relapse-free survival (64% vs. 46%, p = 0.04), and control above the clavicles (80% vs. 48%, p = 0.007) were significantly higher in the Adjuvant Radiotherapy Group compared to those in the Surgery Group (5-year figures shown). Conclusion: The use of adjuvant radiotherapy after surgical resection of tongue base squamous cell carcinoma significantly decreased the rate of local-regional recurrence and improved relapse-free survival compared with surgery alone but did not alter cause-specific or overall survival.

Epstein–Barr virus infection and response to radiotherapy in squamous cell carcinoma of the oral cavity

We have retrospectively investigated the presence of Epstein–Barr virus (EBV) DNA in 45 cases of squamous cell carcinomas (SCCs) of the oral cavity using polymerase chain reaction (PCR). We analyzed the association between EBV infection and the clinicopathological characteristics, tumor response to radiotherapy, or prognosis to determine the clinical significance of EBV. EBV DNA was detected in 29 cases (64.4%) of SCCs. No significant differences were observed between the presence or absence of EBV. Our results indicate that EBV infection is not related to tumor response to radiotherapy, or the prognosis of the patients.

Lack of predictive value of potential doubling time and iododeoxyuridine labelling index in radiotherapy of squamous cell carcinoma of the head and neck

Purpose: To investigate the prognostic value of T POT, S-phase time ( T S), iododeoxyuridine (IdUrd) labelling index ( LI) and DNA index with loco-regional tumour control as the end-point. Materials and methods: Iododeoxyuridine was given to 99 patients with squamous cell carcinomas of the head and neck before the start of radiotherapy. The analysis included FCM parameters ( LI, T S, T POT and DNA index, n=87) and LI determined by immunohistology (IHC, n=45). A hybrid T POT was determined by combining the FCM T S and the IHC LI ( n=45). In diploid tumours ( n=39), the FCM LI was underestimated and the FCM T POT was overestimated because the flow cytometer was unable to distinguish between tumour and normal cells. The `tumour LI' was defined as the IHC LI or the FCM LI of aneuploid tumours when a biopsy for IHC evaluation was not available and similarly the `tumour T POT' was determined by the hybrid T POT or the FCM T POT of aneuploid tumours ( n=63). Results: There was good agreement between the IHC LI and the FCM LI for aneuploid tumours, but there was disagreement for diploid tumours. The median tumour T POT was 4.1 days (range 0.6–19.5 days) and the median tumour LI was 12.9% (range 3.1–46.0%). In a univariate analysis there was no prediction of loco-regional tumour control by the LI, the T S or the T POT determined by either of the methods. T-classification, N-classification, clinical stage and tumour diameter were related with loco-regional tumour control, whereas clinical stage was the only parameter that yielded independent prognostic significance in a multivariate analysis. Conclusions: This study does not confirm the significant prognostic value of T POT as indicated in some previous reports. Larger clinical studies are needed to draw final conclusions.

Altered Fractionation in Radiation Therapy for Squamous-Cell Carcinoma of the Head and Neck

Following is a review of altered fractionation in radiation therapy for head and neck cancer. The goals of altered fractionation are to increase local-regional control and/or reduce the risk of late complications. Altered fractionation schedules can be broadly classified as accelerated fractionation and hyperfractionation. Data indicate that some of these schedules, particularly hyperfractionated radiation therapy, offer improved results compared to conventionally fractionated radiation therapy. Most investigators have observed no significant increased risk of late complications with the dose-fractionation schedules described.

TP53 mutation is an independent prognostic marker for poor outcome of radiotherapy in squamous cell carcinoma of the head and neck

TP53 mutation is an independent prognostic marker for poor outcome of radiotherapy in squamous cell carcinoma of the head and neck

Repopulation capacity during fractionated irradiation of squamous cell carcinomas and glioblastomas in vitro

Determination of clonogenic cell proliferation of three highly malignant squamous cell carcinomas (SCC) and two glioblastoma cell lines during a 20-day course of fractionated irradiation under in vitro conditions. Tumor cells in exponential growth phase were plated in 24-well plastic flasks and irradiated 24 h after plating with 250 kV x-rays at room temperature. Six fractions with single doses between 0.6 and 9 Gy were administered in 1.67, 5, 10, 15, and 20 days. Colony growth was monitored for at least 60 days after completion of irradiation. Wells with confluent colonies were considered as "recurrences" and wells without colonies as "controlled." The dose required to control 50% of irradiated wells (WCD50) was estimated by a logistic regression for the different overall treatment times. The effective doubling time of clonogenic cells (T[eff]) was determined by a direct fit using the maximum likelihood method. The increase of WCD50 within 18.3 days was highly significant for all tumor cell lines accounting for 7.9 and 12.0 Gy in the two glioblastoma cell lines and for 12.7, 14.0, and 21.7 Gy in the three SCC cell lines. The corresponding T(eff)s were 4.4 and 2.0 days for glioblastoma cell lines and 2.4, 4.2, and 1.8 days for SCC cell lines. Population doubling times (PDT) of untreated tumor cells ranged from 1.0 to 1.9 days, showing no correlation with T(eff)s. T(eff) was significantly longer than PDT in three of five tumor cell lines. No significant differences were observed comparing glioblastomas and SCC. Increase of WCD50 with time did not correlate with T(eff) but with T(eff) InSF2 (surviving fraction at 2 Gy). The intrinsic ability of SCC and glioblastoma cells to repopulate during fractionated irradiation could be demonstrated. Repopulation induced dose loss per day depends on T(eff) and intrinsic radiation sensitivity. Proliferation during treatment was decelerated compared to pretreatment PDT in the majority of cell lines. Pretreatment cell kinetics did not predict for tumor cell proliferation during treatment.

855 - Postoperative radiotherapy in squamous cell carcinoma of the larynx — Prognostic factors

855 - Postoperative radiotherapy in squamous cell carcinoma of the larynx — Prognostic factors

Comparative evaluation of therapeutic approaches in stage III and IV squamous cell carcinoma of the thoracic esophagus with conventional radiotherapy and endoscopic treatment in combination and endoscopic treatment alone: A randomized prospective trial

To define the role of endoscopic dilatation/intubation and radiotherapy in squamous cell carcinoma of esophagus patients to improve their quality of life. One hundred and four patients with squamous cell carcinoma of the thoracic esophagus having Stage III and IV disease were enrolled in the present study, with 90 patients in Group 1 (nonesophagorespiratory fistula group) and 14 patients in Group 2 (esophagorespiratory fistula group). From Group 1 patients, 47 were subjected to radiotherapy (conventional) and had endoscopic dilatation and/or intubation whenever and wherever required (Group 1a), and 43 patients were allowed to follow the natural course of the disease except palliation with endoscopic dilatation and/or intubation whenever and wherever required (Group 1b). From Group 2, 4 patients received radiotherapy in addition to endoscopic intubation, while 10 patients received only endoscopic intubation. The median survival for Group 1a was 7 months, for Group 1b--3 months, for Group 2a--4.25 months, and Group 2b--3.6 months. Only three patients from Group 1a survived more than 18 months, while no patient from Groups 1b, 2a, or 2b survived for more than 1 year. The difference in survival between Group 1a and 1b was statistically significant. The addition of radiotherapy to endoscopic treatment definitely prolongs survival as well as improves the quality of life of these patients. We recommend both for the adequate palliation of patients with this disease.

An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity

Purpose : To analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity. Methods and Materials : Between October 1964 and November 1993, 134 patients with 135 previously untreated primary invasive squamous cell carcinomas of the oral cavity (excluding the lip) were treated postoperatively with continuous courses of external-beam irradiation at the University of Florida. All patients had a minimum follow-up of 2 years (analysis, December 1995). No patient was lost to follow-up. Results : The 10-year actuarial rates of primary site, neck, and local-regional control were 79%, 88%, and 71%, respectively. Recurrence of cancer above the clavicles developed in 35 patients. Ninety-four percent of the recurrences were within the primary field of irradiation (anterior to the plane of the spinal cord); there were 24 recurrences at the primary site and nine in the upper neck alone. There were no failures in the neck area behind the plane or the spinal cord (i.e., the “posterior strip”). Two failures occurred in the low neck below the level of the thyroid notch. In univariate analyses, factors that affected local-regional control included pathologlc stage (I–II vs. III–IV, p = 0.04), margin status (invasive cancer at the margin vs. other, p = 0.0007), multifocal tumor ( p = 0.05), perineural invasion ( p = 0.04), and number of indications for postoperative irradiation ( p = 0.05). Extracapsular nodal extension was marginally significant ( p = 0.07). In multivariate analysis, positive margins and number of indications remained significant These factors were used to define relatively favorable (< 4 indications, margins not positive) and unfavorable (⩾ 4 indications and/or margins positive for invasive cancer) groups. For both favorable and unfavorable groups, there were nonsigniftcant trends toward improved local-regional control for patients who began irradiation within 45–50 days, compared with those whose irradiation began later. There were also nonsignificant trends toward improved control for patients treated with shorter overall irradiation treatment courses. An analysis was also performed on the effects of duration of the overall “treatment package” (from the date of surgery until the last day of irradiation). For patients with unfavorable turners, there was a significantly higher probability of local-regional control for patients whose overall “treatment package” was ⩽ 100 days (60% vs. 14%, p = 0.04). The 5-year rate of distant metastasis as the sole site of failure was 8% and was predicted by pathologic N stage (N0–N1, 3%; N2–N3, 16%, p = 0.02), as well as the presence (20%) or absence (6%) of extracapsular nodal extension ( p = 0.06). The 5-year freedom-from-relapse rate was 63%. The 5-year survival and cause-specific survival rates were 50% and 67%, respectively. Four severe radiation injuries occurred (3%). Conclusion : This paper provides data that define relatively favorable and unfavorable groups of patients in the postoperative setting. Patients with four or more indications for irradiation andlor invasive cancer at the surgical margins have a worse outcome than patients who do not have these negative factors; this is true in spite of the fact that the unfavorable group received higher doses of radiation. Attention should be focused on not only the interval between surgery and irradiation, but also time-dose parameters and the overall duration of the treatment “package.”

Preoperative combined cisplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity—evaluation of more than 5-year follow up cases

Preoperative combined cisplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity—evaluation of more than 5-year follow up cases

2122 The clinical significance of postoperative irradiation for squamous cell carcinoma of the cervix

2122 The clinical significance of postoperative irradiation for squamous cell carcinoma of the cervix

Controlled trials of synchronous chemotherapy with radiotherapy in head and neck cancer: overview of radiation morbidity.

Recently published overviews of randomized controlled trials of simultaneous chemotherapy with radiotherapy in squamous cell carcinoma of the head and neck have demonstrated a significant survival advantage from the combined treatment compared with radiotherapy alone. However, they also showed that chemotherapy increased acute radiation morbidity, but there was no information on late effects. The 19 publications of trials of simultaneous chemotherapy contained in the overview by Munro were reviewed for morbidity data. It was found that chemotherapy significantly enhanced both acute and late effects, suggesting that the drugs may be merely dose-modifying. Future trials should be designed to determine whether or not chemotherapy improves the therapeutic ratio.