Results of radiation therapy in early glottic carcinoma (T1, T2 N0)

Glottic carcinoma is curable by either surgery or radiotherapy. A total of 60 patients were treated by radiation alone at the Northern Israel Oncology Center, Rambam Medical Center, Haifa, between 1970 and 1980. Twenty-nine (48%) were classified as T1 N0 and 31 (52%) as T2 N0. All patients received radiotherapy primarily with curative intent, with surgery reserved for recurrences. The 5-year actuarial survival for all patients was 90% and actuarial disease-free survival was 95%. In ten patients (17%) there was local failure, and five of them were salvaged by surgery. There were no significant acute or long-term complications of radiation. Factors influencing treatment outcome (anterior commissures involvement, degree of differentiation, treatment volume, and technique of irradiation) and the occurrence of second primary malignancies are discussed.     

Radiation therapy in early carcinoma of the glottic larynx T1NOMO

: The Purpose of this report is to present the local control rate and survival of patients treated by radiation therapy for T1N0M0 squamous cell carcinoma of the glottic larynx.

: A total of 41 patients squamous cell carcinoma of the glottis were treated at the Veterans Administration Medical Center Minneapolis, MN, between 1976 and 1990. Of the 41 patients, 40 are available for retrospective analysis with a minimum of a 2-year follow-up and a median follow-up of 5.8 years. Treatment was given to all the patients by a 4 MeV linear accelerator. The vast majority of the patients were treated with bilateral laryngeal opposed wedged 6 × 6 cm fields with a dose of 1.75 Gy per fraction to a total of 70 Gy in 40 fractions over 56 elapsed treatment days.

: The data indicated local control and survival of 92.3% at 2 years and 91.8% at 3 years, post irradiation, with ultimate disease-free survival after surgical salvage of 97.4% and 97.2% at 2 years and 3 years, respectively. These local control and survival rates are comparable to those published in the literature when a higher fractional dose was given. No patients developed notable complications with out technique.

: A dose of 1.75 Gy to 1.8 Gy per fraction to a total of 70 Gy in 56 elapsed treatment days is well tolerated and yields ultimate disease free-survival of 97.2% at 3 years. This time-dose fractionation could be used safely for treating patients who demonstrate low tolerance to irradiation with a risk of laryngitis, laryngeal edema, or difficulty of swallowing, with a higher fractional dose.     

喉部分切除术和经口内镜CO 2 激光显微手术治疗前联合阳性早期声门癌患者的疗效比较

背景与目的：早期声门癌患者虽然发病率不高,但该病对患者语言功能、生活质量等均有明显影响。治疗早期声门癌的临床手术方法较多,不同疗法在不同文献报道中存在较大差异。比较喉部分切除术、经口内镜CO ₂ 激光显微手术分别治疗前联合阳性早期声门癌患者的疗效差异。方法：2015年11月—2018年5月,对张家港市中医医院128例前联合阳性早期声门癌患者进行研究,按住院单双日分为两组,根据治疗方式的不同分为试验组（经口内镜CO ₂ 激光显微手术）和对照组（喉部分切除术）,每组64例。比较两组患者治疗前后吞咽功能和生活质量评分、患者治疗前后嗓音声学指标、临床资料、临床疗效的差异。结果：试验组患者基频微扰（Jitter）、振幅微扰（Shimmer）指标显著低于对照组患者（P<0.05）,试验组患者标准规范化噪声能量（normalized noise energy,NNE）、谐噪比（harmonics to noise ratio,HNR）指标显著高于对照组患者（P<0.05）;试验组患者标准吞咽功能评定量表（standardized swallowing assessment,SSA）评分显著低于对照组患者（P<0.05）;试验组患者手术时间、术中出血量显著低于对照组患者（P<0.05）;两组患者临床疗效比较,试验组治愈人数显著高于对照组患者（Z=6.671,P=0.036）。结论：经口内镜CO ₂ 激光显微手术相比传统的喉部分切除手术,治疗前联合阳性早期声门癌患者的疗效相对更佳,有助于患者嗓音功能、吞咽功能等的恢复。     

Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index

PURPOSE: Hyperfractionated and accelerated radiotherapy without a split was performed to improve the local control probability of early glottic carcinomas. We analyzed the results of this regimen by using the Ki-67 index. METHODS AND MATERIALS: Over a 12-year period, 85 T1N0M0 glottic cancers and 50 T2N0M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with accelerated fractionation (AF) since 1990. The CF program consisted of five daily fractions of 2 Gy per week, for a total of 64 Gy. The AF program consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, for a total of 55 or 58 Gy. The specimens, taken before radiotherapy, were immunohistochemically stained with anti-Ki-67 antibody. RESULTS: The 5-year local control probability for T1 tumors was 79.6 +/- 6.9% with CF treatment, whereas with AF it was 86.9 +/- 5.6%. For T2 tumors it was 62.7 +/- 12.2% with CF, whereas it was 74.7 +/- 7.8% with AF. The difference between CF and AF did not reach the point of statistical significance. However, when T1 tumors had a Ki-67 index lower than 50%, the local control rate achieved with AF was significantly better than that with CF (p = 0.018). When the tumors had a Ki-67 index that was 50% or more, there was no difference in the local control rate between CF and AF, whether they were T1 or T2. The peak mucosal reactions at the larynx and/or hypopharynx were much more severe and appeared at smaller doses and earlier in AF than in CF. The patients with AF showed no severe late complications. CONCLUSIONS: AF could not obtain statistically significant improvement in local control probability of T1 or T2 glottic carcinomas.     

Radiation therapy in T1-T2 glottic carcinoma: influence of various treatment parameters on local control/complications

PURPOSE: To evaluate the influence of various treatment parameters on local control as well as complications in T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1975 and 1989, 676 patients with early glottic carcinoma (460 T1 and 216 T2) received curative radiation with three different treatment regimens, as follows: Regimen 1-50 Gy/15 Fr/3 weeks (3.33 Gy/daily) for 192 patients; Regimen 2-60-62.5 Gy/24-25 Fr/5 weeks (2.5 Gy/daily) for 352 patients; and Regimen 3-55-60 Gy/25-30 Fr/5-6 weeks (2-2.25 Gy/daily) for 132 patients. RESULTS: The local control at 10 years was 82% and 57% for T1 and T2 lesions respectively (p = 0.0). For the T1N0M0 group, field size had significant impact on local control with both univariate (p = 0.05) and multivariate (p = 0.03) analysis. For T2N0M0, group field size (p = 0.03) as well as registration year (p = 0.016) were significant in univariate analysis whereas only field size remained significant on multivariate analysis. Persistent radiation edema was noted in 146 (22%) patients and was significantly worse with larger field size (p = 0.000) but not related to different treatment regimens. CONCLUSION: The shorter fractionation schedule had comparable local control, without increased complications in comparison to the protracted schedule and is best suited for a busy department.     

Clinical radiobiology of glottic T1 squamous cell carcinoma

Purpose: Radiation therapy is the treatment of choice for early glottic squamous cell cancer in many institutions over the world. Despite a relatively homogenous clinical model of T1 glottic tumors for the fractionation studies, the relationships between dose-time parameters remain unclear. To analyze the influence of fractionation parameters and hemoglobin level on tumor cure, this study has been performed.Materials and Methods: This is a retrospective review of 235 patients with T1N0M0 glottic cancer treated by radiation therapy alone given in a conventional schedule with 5 fractions each week. The individual total dose, dose per fraction, and overall treatment time (OTT) ranged from 51–70 Gy, 1.5–3.0 Gy, and 24–79 days, respectively. The median follow-up was 48 months. Patient data—total dose, dose per fraction, OTT, and hemoglobin level (Hb) measured before the radiation treatment—were fitted by the mixed LQ/log-logistic model.Results: The 5-year local relapse-free survival rate was 84%. All parameters included in the mixed LQ/log-logistic model improved the fit significantly. The dose–response curve for 235 patients with T1 glottic cancer was well defined and steep, and showed significant decrease in tumor control probability (TCP) when total doses were below 61 Gy. The 10-day prolongation of OTT, from 45 to 55 days, decreased the TCP by 13%. The dose of 0.35 Gy/day, compensated repopulation during the 1 day of prolongation, which indicates a potential doubling time (T_pot) for glottic T1 tumor clonogens of 5.5 days. The drop of Hb level of 1 g/dl (from 13.8 g/dl to 12.8 g/dl) gave a 6% decrease of TCP, provided that OTT was 45 days.Conclusion: The significant correlation between the total dose, overall treatment time, hemoglobin concentration, and tumor control probability has been found for T1 glottic cancer.     

T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy.

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure. PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for >or= 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up. RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications. CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.     

Results of definitive radiotherapy in T1 and T2 glottic carcinoma: Institute of Rotary Cancer Hospital experience

Early glottic carcinomas (T₁ and T₂) constitute only 2% of all laryngeal cancers in our data. Seventy patients were seen between 1985 and 1992. All patients were treated by cobalt-60 small field radiotherapy using a beam directed shell. The total dose delivered was 60–65 Gy in 31 patients and 66–70 Gy in 39 patients. The follow-up period ranged from 5 to 126 months, with a mean follow up of 37 months overall and 55 months in the surgical salvage group. Radiation therapy controlled disease in 71% (50 of 70) of patients overall; 75% with T₁ and 67% with T₂ lesions. Total laryngectomy as salvage surgery was performed in 70% (14 of 20) of patients whose disease recurred. Ultimate control including surgical salvage occurred in 64 (91%) of 70 patients in the present study. The actuarial 5 year survival was 83 and 80% in T₁ and T₂ tumours, respectively (statistically insignificant). This report supports the policy of definitive irradiation, reserving surgical salvage for radiation failures in early laryngeal cancers.     

钬激光治疗浅表性膀胱移行细胞癌68例

目的 探讨钬激光治疗膀胱移行细胞癌的临床效果. 方法 2001年10月至 2005年10月采用 Versa Pulse Power Suite Holmium Lase 100 W钬激光,膀胱镜下用钬激光光纤以脉冲能量10～15 J、频率15～40 Hz、功率15～40 W治疗经病理确诊的膀胱移行细胞癌患者68例.男62例,女6例.所有肿瘤均为T1期,G1～G2级.结果 68例患者均用钬激光顺利去除肿瘤.操作时间5～60 min,平均20 min.术中无严重出血、膀胱穿孔及闭孔神经反射.67例获随访,随诊时间1～35个月,7例膀胱肿瘤复发,再次行钬激光治疗顺利. 结论 膀胱镜下用钬激光治疗膀胱肿瘤操作简单、副反应少、安全有效.     

T1N0/T2N0 glottic carcinoma: A comparison of two fractionation schedules

The aim of this paper is the retrospective comparison of accelerated/hypofractionated radiotherapy regimen (AHFX) with standard fractionation regimen (SFX) for patients with early glottic carcinoma. One hundred and forty‐five patients with T₁–T₂ glottic cancer between 1986 and 1998 were eligible. Before 1992, patients received 60–66 Gy in 30–33 fractions over 6–6.5 weeks (SFX) with ⁶⁰Co and 6‐MV beams. After 1992, patients received 52.5–55 Gy in 20 fractions over 4 weeks (AHFX) using 6‐MV beams. The end‐points were overall survival, laryngectomy‐free survival (LFS), loco‐regional control and toxicity. One hundred and two were stage T₁N₀; 43 were stage T₂N₀. Median follow up was 4.9 years. The 5‐year overall survival was 78%. Five‐year loco‐regional control in T₁N₀ patients was higher in AHFX than in SFX group (95 vs 75%, P = 0.002). Loco‐regional control in T₂N₀ patients was similar for AHFX and SFX (81 vs 80%, P = 0.813). Overall LFS was 88%. T₁N₀ AHFX patients had 5‐year LFS of 95% compared with 75% for SFX (P = 0.003). For T₂N₀ AHFX patients, overall LFS was 92% compared with 80% for the SFX group (P = 0.291). No grade 4 or 5 late toxicity occurred. One AHFX patient developed grade 3 toxicity; two of 51 SFX patients developed grade 2 toxicity versus five of 94 AHFX patients. AHFX using 6‐MV beams for treatment of early glottic cancer resulted in equivalent LFS and toxicity when compared with SFX.     

The heterogeneity of the T2 glottic carcinoma and its local control probability after radiation therapy

The definition of T₂ glottic carcinoma permits heterogeneity, which is implied in the literature by the varying local control probability ranging from about 40% to 80% for these tumors. In a prospective series of 59 consecutive patients with T₂ glottic tumors, the local control probability has been evaluated for two hypothetical subdivisions, one with relatively small tumors and the other with tumors of larger volume. The local control probability at 2 years appears to be significantly different, 96% as opposed to 65 %, for the above subdivisions. Dose response analysis has been made. The T2 tumors with small volume have a flat response curve below 7000 rad, whereas tumors with larger volume appear to have responded better with doses above 7000 rad.     

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications

This is an analysis of 304 patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy at the University of Florida between October 1964 and December 1984. All patients had a minimum 2-year follow-up and 82% had at least 5 years of follow-up. Patients were excluded from the analysis of local control if they died within 2 years of treatment with the primary site continuously disease-free; all patients were included in the analysis of treatment complications. Patients were staged according to the 1983 AJCC system. Stage T2 was subdivided into 2 groups as follows: T2a (normal mobility) and T2b (decreased mobility). The rates of local control with radiation therapy were as follows: T1, 159/171 (93%); T2a, 50/65 (77%); and T2b, 31/43 (72%). Patients were further divided into subsets based on T stage and the surgical procedure that would have been required to resect the lesion. Local control was noted to improve with higher doses and dose per fraction in 4 of 7 subsets. In 2 of 3 subsets where a dose-fractionation relationship was not observed, there were no local recurrences in 1 subset and only 2 local recurrences in the other. The overall incidence of serious complications was 5/304 (1.6%) and was associated with T stage and with increasing total dose and dose per fraction.     

Radiation therapy of T1N0M0 glottic carcinoma: clinical evaluations based on field size, plastic shell and wedge filter

One hundred forty previously untreated cases of T1N0M0 glottic carcinoma underwent therapy at our department from November 1977 through May 1984. Ninety-six of them were treated with the open-field technique of 4 MVX-ray using parallel opposed fields in bandage up to April 1982 (group I). The remaining 44 cases were treated with the wedge-filtered technique in a plastic shell in order to improve the dose distribution and immobilization during radiotherapy starting in May 1982 (group II). The two-year disease-free survival rates were 85% and 91%, respectively. Thus, better results were achieved by improved treatment techniques.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.     

Clinical phase I trial of concurrent chemo-radiotherapy with S-1 for T2NO glottic carcinoma

We conducted a phase I study to determine a recommended dose (RD) of S-1 for chemo-radiotherapy consisting of S-1+ radiotherapy for T 2 N 0 larynx cancer. The method of administration used to assess the RD was irradiation with 2 Gy/day for 5 days a week until a total dose of 60 Gy, and concomitant administration of S-1 once a day for 2 weeks beginning on the day therapy was started followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body/day (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). 18 patients were enrolled. 4 patients developed an adverse event of grade 3 radiation dermatitis which became a dose-limiting toxicity (DLT) at level 3. We then concluded that 100 mg/body/day was the maximum tolerated dose (MTD) of S-1 and decided that the RD of S-1 was 80 mg/body/day.     

Total resection of glans penis surface by CO2 laser microsurgery

Fifteen patients underwent resection of the whole glans surface with laser microsurgical technique from May 1983 to September 1987. The operations were performed in one stage in 11 cases and in two stages in 4. In 3 cases the resected lesions represented multiple dysplasia grade III or carcinoma in situ, in 1 case hyper/parakeratosis and penile horn, and in 11 cases superficial squamous cell carcinoma. In 8 cases primary superficial and flat tumors occupied more than half the circumference of the organ, and in the remaining 7 cases there were flat, superficial residues after systemic chemotherapy for exophytic, non-infiltrating carcinomas. The CO2 laser beam was used under constant microscopic visual control at a mean output power of 20W, CW or pulsed for the tissue excision from the meatus to the sulcus level. Maximum depth of resection was 2.6 mm. Postoperative external radiotherapy (60 Gy) was given in the first case of the series (microscopically invasive cancer). Satisfactory cosmetic and functional results were observed in all cases. During the follow-up period, ranging from 2 to 48 months, persistent cancer was found at the perimeatal area in 1 case 4 months after laser resection. The procedure can be considered for conservative treatment of wide or multiple superficial lesions of the glans penis.     

Surgical salvage therapy: abdominoperineal resection for recurrent anal carcinoma, metastasectomy of recurrent colorectal cancer, and esophagectomy after combined chemoradiation

This review highlights the advances in the salvage surgical therapies for recurrent disease after definitive therapy of anal carcinoma, colorectal cancer, including liver metastasectomy, and esophageal carcinoma treated primarily with chemoradiation. New diagnostic modalities, advances in neoadjuvant therapies for unresectable liver metastases, and, in addition, the importance of adjuvant hepatic arterial chemotherapy after curative liver resections are reviewed. Although chemoradiation is not the standard of care for esophageal cancer, salvage esophagectomy after such treatment is discussed. Definitive chemoradiation for squamous cell carcinoma of the anus has altered the role of surgical intervention to a salvage option instead of primary treatment. Although this is not yet the case for esophageal carcinoma, recent improved chemoradiation regimens have been reported by the French and Japanese, who use surgery for nonresponders. For recurrent colorectal carcinoma, including liver-only metastases, patients can be rendered disease free after surgical extirpation with evidence of improved survival. Appropriate surveillance in these patients may identify subsets of patients with disease amenable to resection.     

Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome.

BACKGROUND AND PURPOSE: Assuming that the dose-response curve for T3N0M0 glottic carcinoma is steep and that the rate of occult lymph node metastases is low, it should be possible to employ high biological tumour doses to modest target volumes and thereby maximise laryngeal control without compromising final neck control. Within the constraints of a retrospective study we aim to examine this policy with respect to local control, incidence of nodal relapse and late complications. MATERIALS AND METHODS: One hundred and fourteen patients with T3N0M0 glottic carcinoma who received a 3-week schedule of radical radiotherapy between 1986 and 1994 were analysed. The median age was 67 years (range, 34-85 years) and the median follow-up for living patients was 4.8 years (1.9-8.9 years). There were no strict selection criteria for those patients treated with radiotherapy. RESULTS: The 5-year overall survival was 54%. The 5-year local control with radiotherapy and the ultimate loco-regional control following salvage laryngectomy were 68 and 80%, respectively. Nine patients (8%) suffered a regional nodal relapse but only three of these (3% overall) occurred in the absence of local failure. Four patients (3.5%) developed serious late complications requiring surgical intervention (three received 55 Gy and one 52.5 Gy). CONCLUSIONS: It is possible to employ maximum tolerable doses to specific target volumes and thereby exploit the dose response demonstrated and minimise major late effects. The use of modest target volumes resulted in only 3% of patients requiring surgery that might have been avoided had prophylactic neck irradiation been employed.