Consensus study on the health system and patient-related barriers for lung cancer management in South Africa.

BACKGROUND: Lung cancer is the highest incident cancer globally and is associated with significant morbidity and mortality particularly if identified at a late stage. Poor patient outcomes in low- and middle-income countries (LMIC's) might reflect contextual patient and health system constraints at multiple levels, that act as barriers to prevention, disease recognition, diagnosis, and treatment. Lung cancer screening, even for high-risk patients, is not available in the public health sector in South Africa (SA), where the current HIV and tuberculosis (TB) epidemics often take precedence. Yet, there has been no formal assessment of the individual and health-system related barriers that may delay patients with lung cancer from seeking and accessing help within the public health care system and receiving the appropriate and effective diagnosis and treatment. This study aimed to derive consensus from health-system stakeholders in the urban Gauteng Province of SA on the most important challenges faced by the health services and patients in achieving optimum lung cancer management and to identify potential solutions. METHODS: The study was undertaken among 27 participant stakeholders representing clinical managers, clinicians, opinion leaders from the public health sector and non-governmental organisation (NGO) representatives. The study compromised two components: consensus and engagement. For the consensus component, the Delphi Technique was employed with open-ended questions and item ranking from five rounds of consensus-seeking, to achieve collective agreement on the most important challenges faced by patients and the health services in achieving optimal lung cancer management. For the engagement component, the Nominal Group Technique was used to articulate ideas and reach an agreement on the group's recommendations for solution strategies and approaches. RESULTS: Public health sector stakeholders suggested that a lack of knowledge and awareness of lung cancer, and the apparent stigma associated with the disease and its risk factors, as well as symptoms and signs, are critical to treatment delay. Furthermore, delays in up-referral of patients with suspected lung cancer from district health care level were attributed to inadequate knowledge arising from a lack of in-service training of nurses and doctors regarding oncologic symptoms, risk factors, need for further investigation, interpretation of x-rays and available treatments. At a tertiary level, participants suggested that insufficient availability of specialised diagnostic resources (imaging, cytological and pathological services including biomolecular assessment of lung cancer), theatres, cardiothoracic surgeons, and appropriate therapeutic modalities (chemotherapeutic agents and radiation oncology) are the main barriers to the provision of optimal care. It was suggested that a primary prevention programme initiated by the government that involves private-public partnerships may improve lung cancer management nationally. CONCLUSIONS: Considerable barriers to the early identification and treatment of lung cancer exist. Finding solutions to overcome both individual and health-system level obstacles to lung cancer screening and management are vital to facilitate early identification and treatment, and to improve survival. Furthermore, research on inexpensive biomarkers for asymptomatic disease detection, the introduction of diagnostic imaging tools that utilise artificial intelligence to compensate for inadequate human resources and improving clinical integration across all levels of the healthcare system are essential.

The spectrum of human immunodeficiency virus-associated cancers in a South African black population: results from a case-control study, 1995-2004.

The effect of the evolving HIV epidemic on cancer has been sparsely documented in Africa. We report results on the risk of cancer associated with HIV-1 infection using data from an ongoing study. A case-control analysis was used to estimate the relative risk (odds ratio, OR) of cancer types known to be AIDS defining: Kaposi's sarcoma (n = 333), non-Hodgkin lymphoma (NHL, n = 223) and cancers of the cervix (n = 1,586), and 11 cancer types possibly associated with HIV infection: Hodgkin lymphoma (n = 154), cancers of other anogenital organs (n = 157), squamous cell cancer of the skin (SCC, n = 70), oral cavity and pharynx (n = 319), liver (n = 83), stomach (n = 142), leukemia (n = 323), melanoma (n = 53), sarcomas other than Kaposi's (n = 93), myeloma (n = 189) and lung cancer (n = 363). The comparison group comprised 3,717 subjects with all other cancer types and 682 subjects with vascular disease. ORs were adjusted for age, sex (except cervical cancer), year of diagnosis, education and number of sexual partners. Significantly increased risks associated with HIV-1 infection were found for HIV/AIDS associated Kaposi's sarcoma (OR = 47.1, 95% CI = 31.9-69.8), NHL (OR = 5.9, 95% CI = 4.3-8.1) and cancer of the cervix (OR = 1.6, 95% CI = 1.3-2.0); Hodgkin's disease (OR = 1.6, 95% CI = 1.0-2.7), cancers of anogenital organs other than the cervix (OR = 2.2; 95% CI = 1.4-3.3) and SCC (OR = 2.6, 95% CI = 1.4-4.9) were also significantly increased. No significant associations were found between HIV and any of the other cancers examined. Risks for HIV-related cancers are consistent with previous studies in Africa, and are lower when compared to those observed in developed countries.

Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma--a prospective randomized trial.

PURPOSE: To compare a conventional fractionation regimen with a hypofractionated regimen in the treatment of Epidemic Kaposi sarcoma with radiation therapy. MATERIALS AND METHODS: Sixty patients were randomized to receive a standard regimen of 24 Gy in 12 fractions (ARM A) or the study regimen of 20 Gy in five fractions (ARM B). Radiation technique was individualized. Treatment response, local control and toxicity were recorded. RESULTS: Thirty five sites were treated in ARM A and 30 sites in ARM B. Treatment arms were similar for gender, ECOG performance score, treated site, antiretroviral therapy usage, T stage, I stage and S stage. The overall survival using the Kaplan Meier method was 37% at 1 year. Complete responses were recorded at 28 sites (13 Arm A,15 Arm B), partial responses at 19 sites (8 Arm A,11 Arm B) and stable disease at three sites (2 Arm A,1 Arm B). The mean time to maximum objective response was 3 months (range: 1-14 months). Response rates and local control were equal in the two arms (p=0.73 and 0.77, respectively, log rank test). Acute skin toxicity (p=0.77) and late skin toxicity (p=0.24) were equal in the two arms. CONCLUSION: The two treatment regimens produced equivalent results for treatment response, local recurrence-free survival and toxicity.

A prospective analysis of high-dose-rate endobronchial brachytherapy in the palliation of obstructive symptoms in lung cancer patients: A single-institution experience.

PURPOSE: Obstructive symptoms that affect quality of life (QOL) are commonly caused by endobronchial disease in many patients with locally advanced, inoperable lung cancer. High-dose-rate endobronchial brachytherapy (HDREBBT) has been used to palliate these symptoms, yet its role is not well defined in the literature. METHODS AND MATERIALS: Ninety-eight patients with locally advanced, inoperable lung cancer received HDREBBT. They were prospectively followed for survival, QOL, and toxicity endpoints. QOL measures were captured using the Quality of Life Questionnaire-Lung Cancer 30 and -Lung Cancer 13. RESULTS: At 1-year follow-up, no significant toxicities were seen. Overall survival was 13.4% at 12 months (mean 192 days). Performance status, additional treatment after HDREBBT and treatment intent affected overall survival on univariate analysis (p < 0.05). Mean hemoptysis-free survival for all patients was 232.3 days, cough-free survival was 140.3 days, and dyspnea-free survival was 173.5 days. There was no impact of any treatment- or patient-related factors of these outcomes on multivariate analysis, including additional treatment modalities and HDREBBT dose. CONCLUSIONS: HDREBBT is a safe and effective way to palliate endobronchial symptoms. Additional external-beam radiation therapy, chemotherapy, or chemoradiation after HDREBBT improves survival, but does not affect QOL measures.

Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study.

BACKGROUND: Previous studies from South Africa have established that fractionated high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation and survival in advanced esophageal cancer. A multicenter, prospective randomized study was therefore conducted under the auspices of the International Atomic Energy Agency to evaluate two HDR regimens. METHODS AND MATERIALS: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score >50, age 17-70 years, primary disease in the thoracic esophagus, no prior malignancy within the past 5 years, and any N or M status were included in the study. Exclusion criteria included cervical esophagus location, tumor extending <1 cm from the gastroesophageal junction, tracheoesophageal fistula, Karnofsky performance score <50, altered mental status, and extension to great vessels on CT. Patients were randomized to receive 18 Gy in 3 fractions on alternate days (6 Gy per fraction, Group A) or 16 Gy in 2 fractions on alternate days (8 Gy per fraction, Group B). The HDR dose was prescribed at 1 cm from the center of the source axis after dose optimization. A margin of 2 cm was included proximally and distally. The respective hospital and university committees gave approval for the study, and all patients provided informed consent. RESULTS: A total of 232 patients were entered into the study (112 in Group A and 120 in Group B). There was no difference between the groups for any of the prognostic variables. All patients were followed until death. The dysphagia-free survival for the whole group was 7.1 months (Group A, 7.8 months; Group B, 6.3 months; p >0.05). The overall survival was 7.9 months for the whole group (Group A, 9.1 months; Group B, 6.9 months; p >0.05). On univariate analysis, the presenting weight (p = 0.0083), gender (p = 0.0038), race (p = 0.0105), the presenting dysphagia score (p = 0.0083), the treatment center (p = 0.0029), and tumor grade (p = 0.0029) had an impact on the dysphagia-free survival, and gender (p = 0.0011) and performance score (p = 0.0060) had an impact on dysphagia-free survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p = 0.0430) and multivariate (p = 0.0331) analysis. The incidence of strictures (Group A, n = 12; Group B, n = 13; p >0.05) and fistulas (Group A, n = 11; Group B, n = 12; p >0.05) was similar in both groups. CONCLUSION: Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers, surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8 Gy x 2 give similar results for dysphagia-free survival, overall survival, strictures, and fistulas and are equally effective in palliation of advanced esophageal cancer.

Randomized prospective study comparing high-dose-rate intraluminal brachytherapy (HDRILBT) alone with HDRILBT and external beam radiotherapy in the palliation of advanced esophageal cancer.

PURPOSE: HDRILBT is one of the best methods of palliation for advanced esophageal cancer (AEC) by improving dysphagia-free survival (DFS) and overall survival (OS). This study examines if the addition of EBRT would further improve the outcome by improving DFS in AEC. METHODS AND MATERIALS: Patients with inoperable AEC were entered into a randomized prospective study. HDRILBT of 16 Gy/2 fractions/3 days was given initially to all patients. Following treatment, patients were randomized to receive no further treatment (Group A) or additional EBRT of 30 Gy/10 fractions/2 weeks (Group B) and were followed for 1 year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the chi(2) and log-rank tests and survival curves were drawn using the Kaplan-Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. RESULTS: Sixty patients were entered into the study. Patient and tumor characteristics were comparable among the groups. Of 30 patients in Group B, 2 refused additional EBRT (no dysphagia). At 6 months, >50% had DFS in both groups and this was comparable. There was no difference statistically (p >0.05) in the DFS and OS between the two groups at the end of 12 months. Median survival for Group A was 7.23 months and 7.5 months for Group B. Additional EBRT did not improve DFS or OS. Eleven patients developed strictures related to radiotherapy and were dilated successfully (Group A, 7; Group B, 4; p >0.05). Four patients had progressive luminal disease which progressed to fistula (Group A, 3; Group B, 1; p >0.05). There was no effect of any patient or treatment parameter on DFS. Presenting weight and ECOG score had an impact on OS. CONCLUSIONS: From the preliminary analysis, additional EBRT to HDRILBT does not improve DFS or outcomes in inoperable AEC.

Adding external beam to intra-luminal brachytherapy improves palliation in obstructive squamous cell oesophageal cancer: a prospective multi-centre randomized trial of the International Atomic Energy Agency.

BACKGROUND: Whether the combination of high dose-rate brachytherapy (HDRBT) and External Beam Radiation Therapy (EBRT) is superior to HDRBT alone for the palliation of oesophageal cancer has only been explored in a previous IAEA pilot randomized trial. METHODS: Two hundred and nineteen patients were randomized to adding EBRT or not, after receiving two fractions of HDRBT within 1 week. Each HDRBT consisted of 8 Gy prescribed at 1cm from source centre. Patients randomized to EBRT received 30 Gy in 10 fractions. The primary outcome was dysphagia-relief experience (DRE). Additional outcomes included various scores, performance status, weight and adverse events. A majority of charts, imaging and radiotherapy plans were externally audited. RESULTS: Median follow-up was 197 days, with a median OS of 188 days and an 18% survival rate at 1 year. DRE was significantly improved with combined therapy, for an absolute benefit of +18% at 200 days from randomization (p=0.019). In longitudinal regression analyses, scores for dysphagia (p=0.00005), odynophagia (p=0.006), regurgitation (p=0.00005), chest pain (p=0.0038) and performance status (p=0.0015) were all significantly improved. In contrast, weight, toxicities and overall survival were not different between study arms. CONCLUSION: Symptom improvement occurs with the addition of EBRT to standard HDRBT. The combination is well tolerated and relatively safe.