The primary treatment of advanced vocal cord cancer: Laryngectomy or radiotherapy?

When different treatment modalities yield equal results in cancer treatment, the least mutilating is preferred. If results are different, however, the survival rate after treatment must be weighed against the quality of life. Considerable controversy exists concerning the primary treatment modality for advanced glottic cancer, with some authors defending surgery (with or without radiotherapy) and others defending radiotherapy as sole treatment, with laryngectomy reserved for local failures. From a group of 102 patients with T3 and T4 tumors, 65 were treated with a laryngectomy. Uncorrected survival at 5 years was 48%, local control was 75%. A group of 35 patients was treated with radiotherapy. Survival was 22% at 5 years, local control 23%, with rescue surgery 37%. These unfavorable results are related to the negative selection of patients for radiotherapy (inoperable, bad cooperation). In 14 patients who were operable but refused laryngectomy the final local control was 53%, with voice preservation in 34%, survival, however, remained low (27% at 5 years). Primary surgery seems to provide better chances for ultimate survival than radiotherapy alone. At the moment, it is not yet clear if a proportion of patients can be selected for whom a more conservative attitude can be allowed, with laryngectomy reserved for poor regression or recurrences after radiotherapy.     

Management of advanced glottic cancer. A 10 year review of the Toronto experience.

This paper presents a detailed retrospective analysis of all patients with glottic cancer (with the exception of early vocal cord cancer) who were seen at the Princess Margaret Hospital from 1965 through 1974. 358 patients with this diagnosis were seen during this time period; Stage T2N0M0 comprised 46% of the total group, T3N0M0 :25%; 13% had nodal disease and 1.5% had distant disease at presentation. 293 patients were treated with radical radiotherapy; surgery was reserved for salvage of persistent or recurrent disease. The local control rate with radical radiotherapy was 66% for Stage T2N0M0, 45% for Stage T3N0M0 and 56% for Stage T4N0M0. 60% of the radiation failures were salvaged by surgery; surgical morbidity was low.The overall tumor control rates for the major stage groupings were 80% for Stage T2N0M0, 69% for Stage T3N0M0 and 63% for Stage T4N0M0. Of the survivors 82.5% of Stage T2N0M0, 65% of Stage T3N0M0 and 90% of Stage T4N0M0 had an intact larynx and natural voice.Essential features of our management policy include moderate (but effective) dose radiotherapy combined with meticulous radiotherapy planning and careful follow-up to identify radiation failures. Our philosophy of treatment and its rationale emphasize preservation of the larynx and natural voice where possible, but without sacrificing survival.     

The importance of vocal cord mobility in T2 laryngeal cancer

In a retrospective study 75 patients with T2 laryngeal cancer treated from 1981 through 1985 were analysed. Of this group 71 patients had a full course of radiotherapy as primary therapy. All 71 patients were given 70 Gy/7 weeks on the primary and 50 Gy/5 weeks on the neck, 2 Gy per fraction. Various prognostic factors for local control and survival were studied. In our patient group we found vocal cord mobility to be an important prognostic factor for ultimate local control and survival. Patients with impaired cord mobility had a significantly worse ultimate local control (76%) than patients with normal cord mobility (98%) and a significantly worse corrected actuarial survival. It is concluded that impaired cord mobility means more advanced disease. Future studies will have to answer the question how to improve the local control rate in patients with impaired cord mobility, for example, by incorporating laryngectomy earlier in the treatment program of those patients who can not be cured by radiotherapy alone or by using innovative radiotherapy protocols.     

Role of radiation in the management of early vocal cord carcinoma

From 1952-1978, 177 patients with epidermoid carcinoma confined to the true vocal cords with normal mobility (T1NO) were treated with radiation alone. Five- and 10-year adjusted actuarial survival rates for all patients were 97 and 95%, respectively. The tumor recurred in the larynx and/or neck in 16% of patients with T1a (one cord involved) and 23% of the patients with T1b (both vocal cords involved) disease. Radiation failures were surgically salvaged in 89% of patients with T1a disease without anterior commissure involvement, in 60% of those with T1a disease with anterior commissure involvement and in 57% of those with T1b disease. Tumor was ultimately controlled in 97% of the patients with T1a and 90% of the patients with T1b disease. Voice was preserved in 93% of the patients with T1a disease and 77% of patients with T1b disease. Of 121 patients evaluated for voice quality, 77% had good and 22% had fair voice, while only one patient had poor quality of voice. Patients with fair or poor quality voice usually had had salvage hemilaryngectomy. We recommend radiation for all patients with early vocal cord carcinoma.     

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. II. The case of T2N0 disease

Purpose: To retrospectively evaluate local control rates, late damage incidence, functional results, and second-tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T2 glottic cancer. Methods and Materials: A total of 256 T2 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia, Istituto del Radio "O. Alberti" (BS) were studied. Cumulative probability of local control (LC), disease-specific survival (DSS), and overall survival (OS) rates were calculated and compared in the different clinical and therapeutic subgroups by both univariate and multivariate analysis. Types of relapse and their surgical salvage were evaluated, along with the functional results of treatment. Late-damage incidence and second-tumor cumulative probability (STP) were also calculated. Results: In the entire series, 3-year, 5-year, and 10-year OS rates were, respectively, 73%, 59%, and 37%. Corresponding values for cumulative LC probability were 73%, 73%, and 70% and for DSS, 89%, 86%, and 85%, taking into account surgical salvage of relapsed cases. Seventy-three percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were larger tumor extent and impaired cord mobility. At multivariate analysis, the same factors retained statistical significance. Twenty-year STP was 23%, with second-tumor deaths less frequent than larynx cancer deaths (20 of 256 vs. 30 of 256). Incidence of late damage was higher in the first decade of accrual (22%) than in the last decade (10%, p = 0.03); the same was true for severe late damage (9% vs. 1.8%). Conclusion: Present-day radical radiotherapy can be considered a standard treatment for T2 glottic cancer. Better results are obtained in patients with less extended disease. Late damage is relatively infrequent, but a careful follow-up is warranted for early detection not only of relapses (because salvage surgery is feasible) but also of second malignant tumors, which constitute a relevant but not the leading cause of death in these patients and are potentially curable.     

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer. METHODS AND MATERIALS: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated. RESULTS: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831). CONCLUSION: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.     

Single vocal cord irradiation: A competitive treatment strategy in early glottic cancer

Introduction

The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI).

Material and methods

The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed.

Results

A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2 mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved.Conclusions: Given the accuracy (1-2 mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.     

The different clinical presentation, behaviour and prognosis of carcinomas originating in the epilarynx and the lower supraglottis

Within the supraglottic larynx, two subregions can be distinguished: the epilarynx and the lower supraglottis. Tumours arising in these structures have very different clinical presentations and prognosis. Management should be adjusted accordingly. Between 1962 and 1977, 325 patients with supraglottic cancer were seen, of whom 317 presented as untreated cases. In 171 patients (54%) the tumour originated in the lower part of the supraglottis. In this group 61% had T1 or T2 lesions, 23% had palpable neck nodes. In 130 of these patients, the initial treatment was irradiation. At 5 years, actuarial survival was 55% (uncorrected) and local control was 77%. The larynx was preserved in 61% of patients. Tumour stage had only limited influence on treatment results, but the presence of neck nodes was very important for prognosis. The best survival rate was observed in patients with T1 or T2, N0 lesions. Epilaryngeal tumours were seen in 146 patients (46% of all supraglottic tumours). In this group, only 40% had T1 or T2 lesions and 47% had palpable nodes. In the 110 patients primarily treated with radiotherapy, uncorrected actuarial survival was 36%, local control was 56% at 5 years. The voice was preserved in 45% of patients. Tumour stage had no influence on prognosis, but the presence of lymph nodes was a very important prognostic discriminant. A dose-response relation was observed in the range between 40 Gy in 4 weeks and 65 Gy in 6.5 weeks, above this dose level no further improvement was observed. It is remarkable that, although the presence of palpable neck nodes at diagnosis is the most important factor determining local control and survival, only in 23 out of 104 local or regional recurrences was the relapse found in the neck nodes. In 75 patients, the primary treatment was a combination of radiotherapy and surgery (40 lower supraglottic and 35 epilaryngeal tumours). Survival at 5 years was 62%, local control 77%. While these results were about equal in both subsites, both survival and local control were higher than in patients treated with radiotherapy alone. In our institute, the complication rate of surgery after preoperative irradiation was low. From our data, it appears that a laryngectomy is to be preferred for all patients with palpable neck nodes and also for all T3 and T4 lesions of the lower supraglottis. Radiotherapy should probably be reserved for small (T1 and T2) tumours of the lower supraglottis and for epilaryngeal cancer without neck nodes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Treatments patterns of vulvar cancer in the elderly

OBJECTIVE: To evaluate treatment patterns of vulvar cancer in patients over 80 years. MATERIAL AND METHODS: Between 1979 and 1999, the Geneva Tumor Registry identified 230 women with vulvar cancer. Treatment of patients over 80 years and younger were compared. Kaplan-Meier analysis was used to determine disease specific cumulative survival. RESULTS: Young women are more likely to present in situ lesions compared to their older counterparts. Majority of vulvar cancers were observed in women >or=80 (p<0.001) at more advanced stages. Elderly women have either no treatment, either unconventional or inadequate treatments. The Mantel-Haentzel analysis shows a 23.4 OR (IC (95%) 2.9-186.6) of not being treated if the patient is over 80. Specific 5-years survival was 93% in stage I, compared to 21% in stage IV. CONCLUSION: Patients over 80 years are diagnosed at more advanced stages. Less aggressive treatments decrease outcome.     

Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer

PURPOSE: To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. METHODS AND MATERIALS: This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (> or =1 cm), close (>0 and <1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. Results: The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. CONCLUSION: The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects.     

Recurrences after irradiation in early vocal cord cancer with literature review

Radiation therapy in early glottic cancer offers an excellent cure rate with preservation of voice. This study is an analysis of 25 (18%) patients who had failures after irradiation. Ten patients were in stage I (T1N0M0) and 15 patients in stage II (T2N0M0). All patients received megavoltage irradiation with an average dose of 6600 rad, 180 to 200 rad per day, 5 days in a week. Of the failures, 15 patients had the tumor controlled by salvage surgery, laryngectomy being the most common surgical procedure. The median time to recurrence was 23 months. A detailed analysis of the failures, along with a literature review, is done in this paper.     

Quality of voice after radiotherapy in early vocal cord cancer

Early glottic cancer (T1, T2N0M0), a disease of the voice box, mainly affects the voice. It can be effectively treated with both surgery and radiotherapy. Preservation of the voice while treating vocal cord cancer is not simply retaining the ability to vocalize. It is the determinant of choice of treatment and quality of life following curative management. Radiotherapy has resulted in excellent control rates with voice preservation and has been the standard of care for many decades. Several patient- (e.g., smoking, age, amount of talking during treatment), disease- (e.g., extent and site of lesion) and treatment- (e.g., radiation field size and dose, voice therapy) related factors adversely affect the quality of voice after radiotherapy. Several studies have evaluated voice quality either subjectively or objectively. Still, little is known about it. Voice quality after radiotherapy improves but does not reach the standard of the normal controls.     

Early glottic cancer: The influence of primary treatment on voice preservation

Retrospective analysis was performed to assess the influence fo primary surgical or irradiation treatment on local control, survival, and final preservation of larynx in comparable groups of patients with T1N0 and T2N0 glottic cancer.

Two hundred sixty-three previously untreated patients with invasive squamous cell carcinoma of the glottis (187T1 and 76T2) were treated with primary radiotherapy (159T1 and 60T2) or primary surgery (28T1 and 16T2) between January 1976 and December 1990, at the University of Ljubljana, Slovenia. Conventional one daily fraction of 2 Gy to doses of 60–74 Gy (median: 65 Gy) were used in 98% of primarily irradiated patients through out the observed period. To enable better comparison between the two treatment groups, primarily irradiated patients were retrospectively stratified by the criteria of suitability for primary voice-sparing operation. Several host, tumor, and treatment parameters were analyzed.

Only the stage of the disease significantly influenced both 10-year recurrence-free and disease-specific survival regardless primary treatment modality (p = 0.0002). In all primary irradiated patients local control was significantly better for those with overall treatment time of less than 48 days (p = 0.007). In patients suitable for voice-sparing operation, local control of primarily operated patients was similar to that of patients primarily irradiated with shorter overall treatment time, which was 93 and 88% for T1 and 67 and 64% for T2 tumors, respectively. Ultimate local control in primary surgery and radiotherapy group was 96 and 96% for T1 and 89 and 88% for T2 tumors, respectively. Equal larynx preservation of 100% in T1 and 90% in T2 patients was achieved in finally cured primarily operated patients and those patients primarily irradiated with a shorter overall treatment time. If treatment time was longer than 48 days, significantly worse final larynx preservation of 84% in T1 and 75% in T2 patients was observed (p = 0.003). In patients unsuitable for voice sparing operation, 87% of T1 and 50% of T2 patients in primary radiotherapy group finally had their larynx preserved.

Stratification based on criteria of possibility for initial voice-sparing operation is important when comparing primary surgery with primary radiotherapy treatment in ealry glottic cancer. The detrimental effect of prolonged treatment time of irradiation resulted not only in inferior local control rate but also in worse final larynx preservation.     

Hypopharyngeal cancer: results of treatment with radiotherapy alone and combinations of surgery and radiotherapy

From 1962 to 1977, 90 patients with hypopharyngeal cancer were seen in the Academic Hospital in Leuven. Radiotherapy was the primary treatment in 66 patients, actuarial survival was 18% at 5 years and local control 22%. In 22 patients treated with a laryngopharyngectomy and pre- or postoperative radiotherapy, survival was also 18%, but local control was obtained in 51%. No differences in prognosis were demonstrated according to the tumoral stage or nodal status. Metastases were found in 10.5% of irradiated patients and in 14% of patients treated with combined therapy. The frequency of postoperative complications was not increased after surgery for preoperatively irradiated patients. Treatment results in hypopharyngeal cancer remain unfavorable, even with a combination of surgery and radiotherapy. Alternative approaches should be actively investigated to improve local control rates such as the modalities currently under study (high LET, new fractionations, combinations with drugs).     

619例喉癌治疗方法的分析

探讨喉癌患者优先选择放射治疗的可行性。方法:回顾性分析1977年1月～1986年12月收治的619例喉癌患者,将其分为3组。首选手术治疗组296例,包括手术失败后补救性放疗98例;首选放射治疗组232例,包括放疗失败后补救性手术41例;术前放疗加手术组91例。结果:全组5年生存率为62.3%;首选手术组,首选放疗组和术前放疗组5年生存率分别为68.9%,61.2%和63.7%,3组比较均P>0.05;手术失败后补救性放疗和放疗失败后补救性手术5年生存率分别为32.7%和53.7%,P<0.05。结论:对于喉癌患者可考虑首选放射治疗,放疗失败后再行手术治疗。     

Treatment of colorectal cancer in the elderly

Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population.     

Are postoperative complications more frequent and more serious after irradiation for laryngeal and hypopharyngeal cancer?

In order to improve local cure rates and survival in patients with head and neck cancer, combinations of radiotherapy and surgery are used. Most reports on such treatment results indicate an improvement with combined therapy. However, it is not clear whether it is best to irradiate before or after surgery. There is disagreement in the literature, whether postoperative complications are more frequent when the irradiation is given prior to surgery. The incidence of postoperative complications was studied in 213 patients who had a laryngectomy for laryngeal or hypopharyngeal cancer. The incidence of major complications was 8.5% after a preoperative dose of 40 or 50 Gy. After rescue surgery for radiation failure this percentage was 32%. In our experience, the incidence of postoperative complications after doses up to 50 Gy/5 weeks is comparable to what can be expected after surgery alone. When higher doses are given, these complications are more frequent. In designing treatment plans, such considerations should be kept in mind.     

Impact of the interval between short-course radiotherapy and surgery on outcomes of rectal cancer patients

AimsPre-operative radiotherapy has proven to reduce local recurrences after curative surgery for rectal cancer. Radiotherapy is generally well tolerated, although postoperative morbidity and mortality was increased in some patients. Current study was undertaken to analyse whether the interval between preoperative radiotherapy and surgery influences post-operative mortality and recurrence for two cohorts.MethodsAll Dutch patients included in the total mesorectal excision (TME)-trial receiving radiotherapy for resectable rectal cancer were included in this study (n = 642). The verification set consisted of all patients receiving short-course radiotherapy for resectable rectal cancer in two radiotherapy clinics in The Netherlands (n = 600). Univariate and multivariable survival analyses for overall survival, disease-free survival, local recurrence-free survival and non-cancer related survival were calculated.ResultsPatients aged 75 years and older treated during the TME-trial showed a worse overall and non-cancer-related survival when surgically treated 4–7 days after the last fraction of radiotherapy. No differences in survival between the interval groups were found in the verification set.ConclusionPresent study found that elderly patients aged 75 years and older operated 4–7 days after the last fraction of radiotherapy had a higher chance of dying due to non-cancer-related causes during the TME-trial as compared to patients with an interval of 0–3 days. In the verification set similar differences could not be confirmed, which could be due to awareness of the clinicians who avoided delayed surgery after radiotherapy since the results have been presented during congresses. A longer than recommended interval between radiotherapy and surgery should be avoided. Besides, the verification set suggests that radiotherapy duration of 7 days is acceptable.     

Clinical management of primary vulvar cancer

Aims

Vulvar cancer is a rare disease with increasing incidence over the last decades. Treatment includes surgical, radio- and chemotherapeutical options; however, due to the low incidence of the disease and the lack of randomised trials many questions regarding indication of different treatment approaches remain unanswered. This article discusses the current literature to elaborate recommendations for the management of primary vulvar cancer in clinical routine.

Methods

We reviewed the available literature on treatment of invasive vulvar cancer with emphasis on therapeutic strategies such as surgery and radio/chemotherapy.

Results

Surgery of the primary tumour and the groins remain the cornerstone of treatment in vulvar cancer with a strong trend towards a less radical approach in early stage disease. Complete vulvectomy was replaced by radical local excision with plastic reconstruction and the sentinel node technique was implemented to avoid the morbidity of complete groin dissection in node negative patients. In patients with advanced primary disease, treatment decisions are still a challenge. Criteria for the indication and performance of chemo/radiotherapy of the vulva/groins/pelvis are still not fully established and vary between different countries and institutions due to the low level of evidence. Often an individualised therapeutic approach aside from guidelines is necessary to treat these patients adequately.

Conclusions

To enable reasonable treatment decisions and avoid unnecessary morbidity, treatment in specialised centres should be intended at any time. Clinical studies performed by several study groups on an international level are urgently needed to further improve therapy.