Читать книгу Hypopharyngeal Cancer - Группа авторов - Страница 46

The natural course of the disease in patient treated for cure or, at least, for the relief of symptoms, is certainly more favourable than that of those who are not suited for, or not willing to accept the adverse effects of treatment. However, treatment results are still considerably less encouraging those who have recently been reported for other subsides of the head and neck region [8].

In 1997, Hoffman et al. [21] reported an estimated 3,000 new cases of hypopharyngeal cancer diagnosed per year in the United States between 1987 and 1991, with a calculated incidence of 1.1 cases per 100,000 people. Synchronous second primary cancers were seen in 7.4% of patients from the 1990 to 1992 period. A history of a previous cancer was obtained from 16.1% of patients from this period. Analysis of outcome was restricted to cases accrued during the 1980–1985 period to permit a follow-up period of 5 years. Approximately one third of patients were never cleared of their disease, one third remained disease free, and one third experienced recurrence. The clinical TNM stage distribution was 10.5, 12.1, 23 and 52.66% for stages I–IV respectively. Four percent had distant metastases at presentation. Based on the study population from 1980 to 1985 the rates of residual, locoregional failure, and metastases were 32.9, 16.8, and 8.8%. The 3-year disease-specific survival was 39%. Regional recurrences (9.6%) were only slightly more common than local recurrence (7.2%) and the development of distant metastases (8.8%). Overall, disease-specific survival rates dropped from 69.6% at 1 year to 39% at 3 years, and then gradually tapered to 33.4% at 5 years, indicating that most deaths due to disease occurred within the first 3 years of diagnosis. When analysed according to anatomic site, patients with postcricoid lesions showed the best 5-year, disease-specific survival (45.4%) compared with posterior wall lesions (36.9%) or piriform sinus lesions (33.6%). The percentage of patients alive at 5 years decreased in a consistent manner as the stage of the disease increased: stage I (63.1%), stage II (57.5%), stage III (41.8%) and stage IV (22%). Analysis of survival according to the type of treatment indicated that the best outcomes occurred among patients treated with surgery only (with 50.4% surviving 5 years) and surgery with irradiation (with 48% surviving 5 years). Survival among patients treated with irradiation alone was 25.8%. Treatment with combined irradiation and chemotherapy resulted in a 5-year survival rate of 14.9%, only slightly better than for patients treated with chemotherapy only (11.1%).

Hall et al. [9] published a retrospective population-based series of 595 patients diagnosed with hypopharyngeal cancer in the period 1990–1999 from multiple centres across the Province of Ontario Canada. Only one third of patients were well at the time of diagnosis, and almost 40% had a significant reduction in performance status. The most common systems that compromised daily living were respiratory, cardiac, peripheral vascular disease and neurological disease with the latter having the highest number of most severe scores (stroke, dementia, and depression). Similar to other studies, they found the rate of alcohol abuse to be very high with over 70% of the patients having a history of heavy alcohol use. There were 4% stage I, 13% stage II, 27% stage III and 57.4% stage IV with 19.5% of cases deemed unresectable for surgery as the initial treatment. Overall, 22.6% of the 494 treated for cure with surgery + radiotherapy or with radiotherapy alone had residual (persistent) disease at the end of initial treatment. Of the 382 free of recurrence at the end of initial treatment, 49.8% relapsed. Of the first relapses, 50.2% included the primary, 34.8% included the neck and 48.7% included distant metastases. Comparing those patients who had primary surgery to those who had initial RT, fewer had recurrences at the primary, more had distant metastases and the incidence of neck recurrence was similar. Three-year overall survival was 27.3%, the 3-year disease-specific survival for those treated for cure was 47% and 5-year disease-specific survival was 35.02%. Comparing the 2 survival curves it was found that 24% of patients who had died by 3 years died of their comorbid diseases or their treatments. Recurrences tended to appear in the first year and 50% of first recurrences included metastases. Overall, 47% of patients were disease free at 3 years, but eventually 64% of patients died of their cancer. Within the first 11.5 months after treatment, half of the patients had experienced recurrence and 50% of first relapses included distant metastases.

Sewnaik et al. [7] reported the results of a population-based study of 893 cases of hypopharyngeal cancer in Holland during the period 1985 to 1994, based on records from the secondary 9 treatment centres that treat patients with head and neck cancer [8]. Eighty percent were males and the average age was 62.2 years. The TNM stage distribution was 4.2, 9.9, 17.3 and 68.5% for stage I–IV respectively. Three percent had metastatic disease at presentation, similar to our study. Treatment included surgery ± RT in 42%, RT alone in 25%, palliative treatment in 15.8% and no treatment in 5.4%.

Eckel et al. [22] reported a series of 228 consecutive cases treated in a single institution in Germany from 1986 to 1997. The mean age was 53 years, which was much lesser than the age mentioned in other series. They reported that 14.9% of their patients were unresectable at presentation, that 75% were stage IV and that 5.7% had metastatic disease at presentation. Sixty percent had surgery with 90% of those receiving postoperative RT.

In a recent survey on outcomes of head and neck cancer care in Europe covering the 1999–2007 time period, 5-year age-standardised relative survival (calculated by dividing the percentage of patients with the disease and who are still alive at the end of the period of time by the percentage of people in the general population of the same sex and age who are alive at the end of the same time period) was the poorest for hypopharynx and the highest for larynx cancers—25% (range 8.4–32.6) and 59% (range 42.8–77.5) respectively. Thirty-six percent of patients were diagnosed in localised stage (14% for hypopharynx; 56% for larynx). Among the different types of head and neck cancers, only hypopharynx showed an overall low survival (25% at 5 years), with survival figures ranging between slightly more than 30 (North Ireland and Italy) and 8% (Bulgaria). This study confirmed the outcome disparities reported in previous papers [23]. Principally, male sex, ageing and living in Eastern European countries act as unfavourable prognostic factors. During the period 1999–2007, 5-year survival for patients with oral cavity, oropharyngeal and hypopharyngeal cancer significantly improved by 3–5% (absolute difference), while for larynx it remained stable. Over the last decade, there has been a substantial improvement in diagnosis, staging and treatment of patients with head and neck cancers, and overall the natural history of these tumours cancers has also evolved. The current management based on multimodality approach is still quite complex and often deals with issues related to morbidity and quality of life. Concurrent chemo-radiation therapy has become one of the standards of care for most patients in many European countries. European age-specific and age-standardised observed 1-, 3- and 5-year relative survival of hypopharyngeal cancer patients in Europe currently is 59.6, 31.8 and 24.6% respectively. Five-year relative survival rates range from 8.4% in Bulgaria to some 25% in Central and Southern Europe and the United Kingdom and up to 32.8% in Northern Ireland [8].

Recent large-scale studies from the United States showed a survival improvement for patients with hypopharyngeal cancer commencing in the 1990s [24, 25]. Treatment of these patients has increasingly included some form of radiotherapy, and a majority of patients were treated non-surgically. The overall improvement in survival was due largely to the group treated with radiation without surgery.

Kuo et al. [24] reported on a total of 3,958 adult patients with hypopharyngeal cancer identified in the US Surveillance, Epidemiology, and End Results database. The incidence of hypopharyngeal cancer decreased from 1973 to 2010 with an average annual percent change (APC) of 22.0% every year (p < 0.05), with little change in patient or tumour characteristics. Treatment with laryngo-pharyngectomy decreased (22.5% APC, p < 0.001), treatment with radiotherapy without surgery increased (12.0% APC, p < 0.001) and treatment with neither surgery nor radiotherapy increased (10.5% APC, p < 0.001) between 1988 and 2010. There was a significant increase in the 5-year overall survival between 1988 and 1990 and between 1991 and 1995 with no other significant temporal trends in survival. The 5-year overall survival rate for patients in our study was 25.5%. The 5-year survival for patients who were excluded because of the presence of distant metastasis was 4.0%. When patients were segregated by the year of diagnosis (1988–1990, 1991–1995, 1996–2000 and 2001–2005), there was a significant increase in the 5-year survival between 1988–1990 and 1991–1995. Otherwise, there were not any significant temporal trends in survival. Although demographics and tumour characteristics of hypopharyngeal patients have been relatively constant over time, our study found a significant change in treatment patterns with a decrease in the rate of laryngopharyngectomies for hypopharyngeal cancers. The changes in treatment modality were similar to what have been reported in laryngeal cancers. Over the same time period for the same cohort of patients, there has not been a decrease in survival, and survival may in fact be improving over time as survival for patients who receive radiotherapy without surgery improves. These findings suggest that the increased reliance on larynx preserving therapy for hypopharyngeal cancers is not associated with a difference in survival [24]. The 5-year survival for patients who presented with distant metastasis was 4.0%.

Newman et al. selected records of 6,647 patients with SCC of the hypopharynx between 1973 and 2003 from the Surveillance, Epidemiology and End Results database for review, with comparison of 1973–1989 and 1990–2003 cohorts. Overall 5-year survival rates for hypopharyngeal cancer had improved. The average survival of hypopharyngeal cancer patients increased to 41.3% in those diagnosed during 1990–2003 from 37.5% in those diagnosed during 1973–1989 (p < 0.0001). Since 1990, there is a new trend towards treatment using radiation without surgery (43.1 increased to 52.1%), combined surgical and radiation therapy is relatively unchanged (43.6 to 41.8%) and fewer patients underwent surgery alone (14 reduced to 7.3%). Those treated with surgical therapy alone experienced decreased 5-year survival (49.3% pre-1990 and 44.5% post-1990, p = 0.04). Combined surgical and radiation therapy yielded the most favourable results with a trend towards survival improvement (46.7% pre-1990 to 49.0% post-1990, p = 0.07). Our analysis indicates that the best survival rates were achieved in the surgery with the adjuvant radiotherapy group. In contrast to the trends reported for laryngeal cancer, we report that survival has improved for patients with SCC of the hypopharynx over the past 3 decades. Treatment of these patients has been done increasingly with some form of radiotherapy, and the majority of patients are now being treated non-surgically. A emergence of a trend away from surgery but towards radiotherapy was evident. The magnitude of this switch was approximately 9%. This trend is consistent with the adoption of an organ-preservation approach [25].