Back and forth between cancer treatment and cancer control programs: Insights from the Cuban experience

Cancer control is a wider concept than oncology, and includes comprehensive actions for prevention, early diagnosis, treatment, services organization, and education, aiming to modify hard indicators such as incidence, mortality rates, and survival at a population scale. Based on these concepts, organized national cancer programs appeared in several countries in the second half of the 20th century. But at the same time, scientific efforts began to modify the landscape of cancer control. Evidence of mortality reductions began to appear, cancer-driving mutations became measurable, many novel drugs were registered, the methodology of clinical trials spread through health systems, targeted drugs and immunotherapy entered into the mainstream of therapeutics, and treatment goals started to shift from cure to chronic control. The implementation and impact of organized interventions for cancer control show variations according to the context of diverse countries, and scientists and health decision makers can learn from studying these diverse experiences. Among the salient features of cancer control in Cuba are the simultaneous development of a primary care network with abundant human resources and a national biotechnology industry with capacity to provide both generic and innovating drugs and diagnostic systems. The program intentionally assumes the goal of accelerating the transformation of advanced cancer into a chronic disease susceptible of long-term control. The implications of this strategy for population interventions and for scientific research are discussed.     

Focal therapy in prostate cancer: A review of seven common controversies

Radical treatments such as prostatectomy and radiotherapy have demonstrated success in terms of biochemical and disease-specific survival for localised prostate cancer. However, whilst the end goal of any cancer treatment is to control or cure disease it must also do so by minimising any side effects that may be experienced by the patient. Focal therapy as a concept aims to redress this established therapeutic ratio by treating areas of the prostate affected by significant disease as opposed to treating the entire gland. However, there are a number of common criticisms of focal therapy – we deem the seven sins – that require further interrogation.     

Measuring population-level cure patterns for cancer patients in the United States

While the life expectancy of cancer survivors has substantially improved over time in the United States, the extent to which cancer patients are cured is not known. Population-level cure patterns are important indicators to quantify cancer survivorships. This population-based cohort study included 8978,721 cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) databases between 1975 and 2018. The primary outcome was cure fractions. Five-year cure probability, time to cure and median survival time of uncured cases were also assessed. All four measures were calculated using flexible parametric models, according to 46 cancer sites, three summary stages, individual age and calendar year at diagnosis. In 2018, cure fractions ranged from 2.7% for distant liver cancer to 100.0% for localized/regional prostate cancer. Localized cancer had the highest cure fraction, followed by regional cancer and distant cancer. Except for localized breast cancer, older patients generally had lower cure fractions. There were 38 cancer site and stage combinations (31.2%) that achieved 95% of cure within 5 years. Median survival time of the uncured cases ranged from 0.3 years for distant liver cancer to 10.9 years for localized urinary bladder cancer. A total of 117 cancer site and stage combinations (93.6%) had increased cure fraction over time. A considerable proportion of cancer patients were cured at the population-level, and the cure patterns varied substantially across cancer site, stage and age at diagnosis. Increases in cure fractions over time likely reflected advances in cancer treatment and early detection.     

Conservative Management of Anal and Rectal Cancer: The role of radiation therapy

The role of irradiation in the management of anal and rectal cancer has changed during the past ten years. in small epidermoid carcinomas of the anal canal (T1 T2) irradiation is in most departments considered the primary treatment, giving a 5-year survival rate of between 60 and 80% with good sphincter preservation. Even in larger tumors, irradiation can still offer some chance of cure without colostomy. Surgery remains the basic treatment of rectal cancer but irradiation is used in association with surgery in many cases. Radiotherapy is of value in the conservative management of cancer of the rectum in three situations; in small polypoid cancers contact x-ray therapy can give local control in about 90%. in cancers of the middle rectum, preoperative external irradiation may increase the chances of restorative surgery and reduce the risk of local relapse. in inoperable patients, external radiotherapy and/or intracavitary irradiation may cure some patients with infiltrating tumors (T2 T3) without colostomy.     

Improved survival time: What can survival cure models tell us about population‐based survival improvements in late‐stage colorectal,ovarian, and testicular cancer?

BACKGROUND: The objective of the current study was to investigate the long-term impact of treatment advances on the survival of patients with late-stage ovarian, colorectal (American Joint Committee on Cancer stage III, men), and testicular cancers by estimating the increase in the percentage cured from their disease and the change in survival time of uncured patients. METHODS: Cause-specific survival data from 1973 to 2000 were obtained from the Surveillance, Epidemiology, and End Results Program. Survival cure models were fit and were used to estimate the gain in life expectancy (GLE) attributed to an increase in the fraction of cured patients and to prolonged survival among noncured patients. RESULTS: Treatment improvement for ovarian cancer resulted in a total GLE of 2 years, and 80% of that GLE was because of an extension of survival time in uncured patients (from 0.9 years to 2.1 years) rather than an increased cure fraction (from 12% to 14%). In contrast, the cure rate rose from 29% to 47% for colorectal cancer, representing 82% of a 2.8-year GLE, and from 23% to 81% for testicular cancer, representing 100% of a 24-year GLE. CONCLUSIONS: The current results suggested that treatment benefits for testicular and colorectal cancer in men with late-stage disease primarily are the result of increases in cure fraction, whereas survival gains for ovarian cancer occur despite persisting disease. Cure models, in combination with population-level data, provide insight into how treatment advances are changing survival and ultimately impacting mortality. Survival patterns reflect the underlying biology of response to cancer treatment and suggest promising directions for future research.     

Temporal trends in the proportion cured for cancer of the colon and rectum: a population-based study using data from the Finnish Cancer Registry

Colorectal cancer is the third most common cancer worldwide and the second most common cancer in Europe. Cumulative relative survival curves for both cancer of the colon and cancer of the rectum generally plateau after approximately 6-8 years. When this occurs, "population" or "statistical" cure is reached. We analyzed data from the Finnish Cancer Registry over a 50-year period using methods that simultaneously estimate the proportion of patients cured of disease (the cure fraction) and the survival time distribution of the "uncured" group. Our primary aim was to investigate temporal trends in the cure fraction and median survival of the uncured by age group for both cancer of the colon and rectum. For both cancers, the cure fraction has increased dramatically over time for all age groups. However, the difference in the cure fraction between age groups has reduced over time, particularly for cancer of the colon. Median survival in the uncured has also increased over time in all age groups but there still remains an inverse relationship between age and median survival, with shorter median survival with increasing age. The reasons for these impressive increases in patient survival are complex, but are highly likely to be strongly related to many improvements in cancer care over this same time period.     

Psychological distress of cancer and clinical trial participation: a review of the literature

The House of Commons Select Committee on Science and Technology 2000 state that currently less than 5% of adult patients with solid tumours are entered into clinical trials. They recommend that increasing the number of adult cancer patients entering clinical trials must become a high priority. Health-care providers need to prepare themselves for this proposed increase in trial participants by assessing the current status of care and implementing changes within the current infrastructure to provide optimal holistic care. Cancer can change a patient's life either for better or for worse. At one extreme, having cancer leads to enhanced appreciation of life and closer bonds with others. However, at the other extreme, cancer combined with its treatment is viewed as an event that evokes distress and emotional anguish taxing the individual's ability to cope. In the last 25 years, owing to the advent of clinical trials, progress has been made in cancer treatment. Clinical trials may be hailed as the saviour to many therapeutic dilemmas. Treatments are now available which can offer patients hope of cure. Nevertheless, many participants may fear, for the purpose of research, that they may be assigned to less than optimal therapy or that their care will be carried out in a sterile scientific atmosphere devoid of humane and personal consideration. These and other reasons may cause unacceptable personal distress that overrides the potential therapeutic gain. Cancer diagnosis coupled with the ramifications of clinical trial involvement can have significant psychological implications. They may trigger the onset of a mood disorder or exacerbate a present symptom. This article will identify mood disorders in the cancer population, focus on the participants' needs in the clinical trial arena and investigate the influence trial participation has on psychological status.     

A randomised trial comparing tamoxifen vs. surgery in patients over the age of 70 with operable breast cancer - Final results after 28 years of follow-up

A final review of a historical trial commenced in 1982 comprising 200 patients aged 70 or over with operable breast cancer randomised to surgery or tamoxifen with crossover on recurrence has shown that at 21-28 years follow-up,all have died from verified causes.43 in the surgical arm and 40 in the Tamoxifen arm died of breast cancer (41.5% in total). 117 patients (58.5%) died of other verified causes unrelated to breast cancer. These patients in effect achieved a cure from breast cancer. The survival curves for both those treated by surgery or Tamoxifen are similar as are the associated curves comparing deaths from breast cancer and other causes. However although 50% of deaths from breast cancer occurred within the first five years of follow-up, further deaths from breast cancer occurred up to 25 years later. Thus at long term follow-up in a highly selected and favourable group of patients recurrence and death from breast cancer still occurred. This confirms the view that at no time in the post treatment period can one state that any patient is cured of breast cancer. However with favourable patient presentation and optimal current treatment there is a high probability that in a significant number of patients a personal cure will be achieved as described by Brinkley and Haybittle.     

乳腺癌手术术式的选择

  根据乳腺癌的生物学特性，探讨乳腺癌手术方式的变迁。回顾分析25年的乳腺癌手术情况，复习文献资料，提出乳腺癌手术方式的选择原则。乳腺癌改良根治术是基础医院的首选术式，保乳综合治疗在基础医院推广尚需一定时间。乳腺癌手术强调个体化、人性化、微创化、合理化，以手术为主的综合治疗远期疗效好。     

早期喉癌与声带癌前病变的诊断及微创治疗

恶性肿瘤的早期诊断与早期治疗，因其有极高的治愈率和最大限度地保留器官的功能而在临床上愈来愈受到重视。近年喉显微技术的应用，为声带恶性肿瘤及癌前病变的早期诊断和微创伤治疗，创造了必要条件。然而早期喉癌与癌前病变的诊断、病程的演变、治疗措施等至今仍无统一的看法。该文结合中日友好医院1986年－1996年间接受治疗的早期喉癌和癌前病变的诊断分类和微创伤治疗进行讨论。     

Chemotherapy for brain metastases of lung cancer: A review

In lung cancer patients brain metastases develop with a high frequency. For years radiotherapy has been the standard treatment for these patients. Here we review the experience with chemotherapy for brain metastases in lung cancer patients. The concept of the brain as pharmacological sanctuary site when brain metastases are present is challenged and it is argued that chemotherapy does play a role in this situation. Recent clinical trials indicate that the combination of chemotherapy and radiotherapy may become the standard treatment for lung cancer patients with brain metastases. It is unclear whether for micrometastatic disease to the brain, blood brain barrier function is of importance for the outcome of chemotherapy in lung cancer patients with respect to the development of overt brain metastases. Areas of improvement of delivery of cytotoxic agents to the brain when brain metastases have not yet developed are discussed.     

The expanding role of PET technology in the management of patients with colorectal cancer.

The therapeutic options and subsequent survival of colorectal cancer (CRC) patients has increased substantially over recent years. While surgical excision of the primary cancer results in cure of approximately 50% of patients, recurrence and metastatic disease still remains a significant cause of death. Although resection of liver or lung metastases can result in cure, relapse rates remain high, indicating that patient selection needs improvement. Positron emission tomography (PET) technology has a great deal to offer with respect to CRC management, particularly in the setting of patient selection for metastasectomy and in the evaluation of possible recurrent disease, however it has not yet become a routine part of the management of all CRC patients. This review article aims to discuss the current and future implications of PET technology in the optimal management of CRC patients throughout their care pathway.     

Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.     

T2 glottic cancer: An analysis of dose-time-volume factors

Two hundered and forty-four patients with T2NOMO glottic cancer seen at the Princess Margaret Hospital between 1965 and 1977 are analyzed with repsect to the influence of dose-time-volume factors on control of this stage of disease by radiotherapy. Sixty-seven percent of the patients are alive and well five years following treatment; 16% died as a result of glottic cancer and 17% died from intercurrent disease in the five years following treatment. The local control rate by radiotherapy was 72% at three years and 69% at five years. The local control rate by radiotherapy was 80% at five years with a mobile vocal cord and 52% at five years when the cord mobility was impaired (P - 0.0005). An increase in field size from less than 36 cm² to greater than 36 cm² resulted in an improvement in local control by radiotherapy from 57–70 %. This improvement was confined to the normal mobility group (62% local control versus 83% ). Local control was 53% for the overall group when a nominal standard dose (NSD) of less than 1650 ret was used compared to 81% in the 1650–1699 ret group (P - <0.05). This improved local control versus increasing NSD occurred in both the normal mobility and impaired mobility subgroups of patients in this stage of glottic cancer. On the basis of the data presented, a dose cure curve for T2 glottic cancer was derived and compared to previously obtained dose cure curves for T1 and T3 glottic cancer and the dose complication curve for the larynx. The optimal dose-time-volume factors for T2 glottic cancer are discussed.     

Measurement of quality of life in advanced breast cancer

Before the twentieth century the treatment of advanced breast cancer comprised either willful neglect or futile mastectomy. Recent years have seen the introduction of therapies capable of shrinking disease volume although the concept of a cure still remains remote. Many of these treatments are unpleasant and the burden they force the patient to bear may not be compensated by the reduction in tumour size. Decisions on the value of initiating or continuing such treatment have been taken by the clinician largely since no suitable instruments have been available to measure individual 'quality of life'. Several means have now evolved and in advanced breast cancer, where the treatment may profoundly affect the patient's sense of wellbeing, effort is being made to find out how much.     

Novel Directions in Adjuvant Chemotherapy for Early Stage Epithelial Ovarian Cancer

Treatment of early stage ovarian cancer remains controversial despite advances in chemotherapeutic options.Over the past 30 years, molecular and clinicopathologic studies accelerated and treatment of ovarian cancer hasundoubtedly improved although there is a debate as to whether this impacts outcome or not. More recently, theintroduction of targeted therapy started a new era. Probably it is because early stage disease comprises a smallportion of the epithelial ovarian cancer, studies have mostly ignored this group and still there is no clear consensusregarding systemic treatment of early-stage lesions. However this group of patients has the best chance of cure.In this review, we focus on current developments in the treatment of early stage ovarian cancer and query theoptions.     

前列腺癌根治术后生化复发的诊治进展

前列腺癌根治性治疗（根治性手术或根治性放疗）是治愈局限性前列腺癌最有效的方法之一,但是20%的患者在术后5年内发生了生化复发,术后10年内仍有27%-53%的患者发生肿瘤局部复发或远处转移。因此生化复发患者的早期发现、正确评估和规范化治疗,对前列腺癌患者的总体治疗水平尤为重要。     

基因分型对乳腺癌诊治和预后判断的指导作用

乳腺癌是女性的常见恶性肿瘤之一,其临床治疗主要是以经典的TNM和临床分期为指导。近年来兴起的对乳腺癌相关的分子遗传学研究取得了令人瞩目的进展,提出了乳腺癌基因分型这一新概念。基因诊断对乳腺癌的辅助化疗以及预后的判断相对传统的病理分型有更高的专一性,为乳腺癌的治疗起到了更好的指导作用,本文主要对基因分型进行介绍并总结了几种与乳腺癌预后相关的基因标志,探讨其在临床治疗中的实际应用。     

Role of radiotherapy in oligometastatic breast cancer: Review of the literature

Metastatic breast cancer has been historically considered as an incurable disease. Radiotherapy (RT) has been traditionally used for only palliation of the symptoms caused by metastatic lesions. However, in recent years the concept of oligometastatic disease has been introduced in Cancer Medicine as a clinical scenario with a limited number of metastases (≤ 5) and involved organs (≤ 2) with controlled primary tumor. The main hypothesis in oligometastatic disease is that locoregional treatment of primary tumor site and metastasis-directed therapies with surgery and/or RT may improve outcomes. Recent studies have shown that not all metastatic breast cancer patients have the same prognosis, and selected patients with good prognostic features as those younger than 55 years, hormone receptor-positive, limited bone or liver metastases, a low-grade tumor, good performance status, long disease-free interval (> 12 mo), and good response to systemic therapy may provide maximum benefit from definitive treatment procedures to all disease sites. While retrospective and prospective studies on locoregional treatment in oligometastatic breast cancer demonstrated conflicting results, there is an increasing trend in favor of locoregional treatment. Currently, available data also demonstrated the improvements in survival with metastasis-directed therapy in oligometastatic breast cancer. The current review will discuss the concept of oligometastases and provide up-to-date information about the role of RT in oligometastatic breast cancer.     

Chimioradiothérapie concomitante des cancers infiltrants de la vessie

Until now, radical cystectomy has been considered the most effective treatment for invasive bladder cancer. However it fails to cure more than 50% of patients and can result in a mediocre quality of life. In an effort to improve cure rates, combined modality regimens have been investigated. Despite the preliminary results of early clinical trials, randomized trials have most often failed to show any benefit from neoadjuvant or adjuvant chemotherapy or radiotherapy. One of the major progress brought by radiotherapy has been the wide use of conservative treatment in several cancer, and in the recent years promising results have been published with concomitant radio-chemotherapy. The use of conservative approach in bladder cancer now appears to be a tangible reality for selected patients, but this combined modality have not yet been tested in randomized trials.