Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH METHODS: In March 2011 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3), MEDLINE, EMBASE, DORCTHIM and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of the relevant trials and extracted the data from the included trials. MAIN RESULTS: Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBOT and 1153 to control). With HBOT, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (risk ratio (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11; and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBOT varied with different fractionation schemes. Local tumour recurrence was less likely with HBOT at one year (head and neck: RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix: RR 0.60, P = 0.04, NNT = 5) and five years (head and neck: (RR 0.77, P = 0.01, NNT = 6). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH = 22) with HBOT. AUTHORS' CONCLUSIONS: There is some evidence that HBOT improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBOT is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the studies included demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.

[The mortality from malignant neoplasms in the population of a large industrial city with petroleum-refining and petrochemical enterprises]. / Smertnost' ot zlokachestvennykh novoobrazovanii naseleniia krupnogo promyshlennogo goroda s neftepererabatyvaiushchimi i neftekhimicheskimi prepriiatiiami.

Air pollution with toxic chemical near oil-processing and petrochemical enterprises is significantly higher than in administrative district of the city. The studies proved that level and share of mortality with malignancies of trachea, bronchi and lungs is higher in industrial district, than that in the administrative one. The standardized parameters of mortality among females were increased in the industrial district, especially in 70s and 80s, i.e. in 10-20 years after launching the plants. The industrial district was characterized by higher mortality at young age. The mortality with the studied cancers at age of 20-29 and 30-39 prevailed in the industrial district.

[Treatment of malignant tracheo-bronchial tumors. The lost generation]. / Le traitement des tumeurs malignes trachéo-bronchiques. La génération perdue.

250,000 new cases of endobronchial carcinoma are diagnosed each year in France. Risk factors are well known: 80-90% are related to smoking. With an overall 5-year survival rate of only 10%, preventive measures must be our number one priority, especially for young patients, but are their parents a lost generation? Curative therapy has made some progress, particularly with surgery, although only 20% of the patients are potential candidates at diagnosis, and chemotherapy, sometimes in combination with radiotherapy for nonoperable patients. Interesting results have also been achieved with gene therapy where direct intratumoral injection of cytokine genes on recombinant adenoviruses has provided response in certain cases. Interventional bronchoendoscopy provides another promising option as demonstrated by Jeanfaivre and Tuchais who report their results with electrotherapy in this issue of La Presse Médicale.

Typical and atypical bronchial carcinoids.

From January 1955 to April 1987 111 patients with bronchial carcinoid were operated on in our department. There were 62 males and 49 females with a mean age of 45.5 years. Preoperative histological diagnosis was achieved in 22 cases, while in five patients, a false positive diagnosis of small cell lung cancer was reported. Fifteen patients required pneumonectomy, 70 had lobectomy, 16 bilobectomy, and four segmentectomy. One patient required tracheal resection, while in another patient the tumour was removed through bronchotomy. Four patients were completely treated with YAG laser phototherapy. There were three postoperative deaths. The following variables were analysed and discussed in order to evaluate their influence on prognosis: (1) size of the tumour, (2) typical or atypical appearance, (3) endoluminal or extraluminal growth, (4) vascular invasion, (5) node metastases. Atypical onset, node metastases and extraluminal invasion are significant factors in worsening the prognosis.

Bronchoscopic phototherapy at comparable dose rates: early results.

Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in the 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant.

Laser therapy in 100 tracheobronchial tumours.

One hundred patients with tracheobronchial tumours were treated with the neodymium YAG (yttrium-aluminium-garnet) or argon laser for symptoms of airways obstruction caused by tumour (59 cases), complete collapse of a lung (17 cases), or recurrent haemoptysis (24 cases). Seventy four of them had relapsed or failed to respond to radiotherapy or chemotherapy and all were inoperable. Objective improvement in results of lung function tests or haemoptysis diary charts was seen in 37 patients with airways obstruction (63%), five (29%) with collapsed lung, and 14 (58%) with haemoptysis. Overall, 68 patients had symptomatic benefit and there was objective improvement in 56. Two deaths occurred in 288 treatment sessions both occurring as a result of asphyxia from minor haemorrhage in patients with advanced cylindromas and critical narrowing of the trachea or single remaining bronchus. In suitable patients with intraluminal tumour laser phototherapy is a valuable addition to conventional treatment.

Radiotherapy and hyperbaric oxygen. Report of a Medical Research Council Working Party.

The M.R.C. Working Party has coordinated randomised clinical trials to assess hyperbaric oxygen as a sensitiser in radiotherapy. 1669 patients were registered in these studies between 1963 and 1976. Hyperbaric oxygen significantly improved both survival and local tumour control after radiotherapy for head-and-neck tumours and for advanced carcinoma of the cervix. In carcinoma of the bronchus there seemed to be some improvement in survival but this was not statistically singificant. In carcinoma of the bladder hyperbaric oxygen has shown no benefit. Centres already equipped with hyperbaric chambers should continue to use them for those types of tumour shown to benefit. Since hyperbaric oxygen treatment makes great demands on medical and other staff, extension of its use must await comparison with other methods for improving radiotherapy which are now being evaluated.