Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?

In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies. We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses. The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population. Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.     

Pre-operative chemo-radiotherapy in locally advanced rectal cancer: Is this the way of future management?

The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T₃–T₄). A total of 31 patients were assessed (28 T₃ and three T₄ tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m² on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4–6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.     

Has the practice of radiation oncology for locally advanced and metastatic non-small-cell lung cancer changed in Canada?

Aim

Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (nsclc) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic nsclc among Canadian radiation oncologists.

Materials and Methods

An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate. The survey consisted of three scenarios focusing on areas of nsclc treatment in which the radiotherapy (rt) regimen that provides the best therapeutic ratio is unclear.

Results

Replies from 41 respondents were analyzed. For an asymptomatic patient with stage iiib nsclc unsuitable for radical treatment, 22% recommended immediate rt, and 78% recommended rt only if the patient were to become symptomatic. Those who believed that immediate rt prolongs survival were more likely to recommend it (p = 0.028). For a patient with a bulky stage iiib tumour and good performance status, 39% recommended palliative treatment, and 61% recommended radical treatment (84% concurrent vs. 16% sequential chemoradiation at 60–66 Gy in 30–33 fractions). Those who believed that chemoradiation has a greater impact on survival were more likely to recommend it (p < 0.001). For a symptomatic patient with stage iv nsclc, 54% recommended external-beam rt (ebrt) alone, 41% recommended other modalities (brachytherapy, endobronchial therapy, or chemotherapy) with or without ebrt, and 5% recommended best supportive care. A majority (76%) prescribed 20 Gy in 5 fractions for ebrt.

Conclusions

Compared with previous surveys, more radiation oncologists now offer radical treatment for locally advanced nsclc. Management of nsclc in Canada may be evidence-based, but perception by radiation oncologists of the treatment’s impact on survival also influences treatment decisions.     

Does asbestos exposure cause non-Hodgkin's lymphoma or related hematolymphoid cancers? A review of the epidemiologic literature

Asbestos exposure has been linked to non-Hodgkin's lymphoma (NHL) and other types of hematolymphoid cancer (HL-CA) in several case reports and epidemiologic studies. This review covers the scientific and medical literature on the issue of whether asbestos exposure is a cause of NHL or other HL-CAs. Studies of animals exposed to asbestos have not shown an increase in NHL or other types of HL-CA. Although some patients with asbestosis have mild immunologic abnormalities, 32 of 35 epidemiologic studies of asbestos exposure in humans are negative for NHL or other HL-CAs. Therefore, it can be concluded that there is no increased risk of NHL or other HL-CAs associated with asbestos exposure.     

Where does chemotherapy stands in the treatment of ampullary carcinoma? A review of literature

Ampullary carcinoma (AC) is a rare gastrointestinal tumor without clear treatment recommendations. The management of this tumor is usually extrapolated from the treatment of pancreatic, biliary duct and intestinal cancers. Few papers have studied the AC as an independent entity and yet succombs to several limitations. These studies were retrospective single institutional experiences with limited sample sizes recruited over a long period of time. Unlike metastatic ACs where chemotherapy is the only recommended option, localized AC once excised may be approached by either chemotherapy alone or concomitant chemoradiation therapy. In this review, we report the overall survival and recurrence factors of more than 1000 patients from all the studies treating exclusively ACs. We also review the medical treatment of this tumor and conclude to the necessity of multi-institutional randomized controlled studies for AC exclusively.     

What is early lung cancer? A review of the literature

The dismal cure rate of patients with lung cancer and the stage shift hypothesis have propelled the interest to perform screening at large, despite that previous randomized clinical trials failed to show any mortality benefit and the controversial issue of overdiagnosis. Due to early detection programs, a larger number of individuals at risk will be found to harbor small and potentially malignant early stage lesions. The application of non- and minimal invasive techniques for early detection, staging and treatment will become increasingly important. This review deals with the available clinical, surgical and pathological data focusing on early lung cancer lesions < or =1 cm. Literature data from both centrally located and parenchymal lesions < or =3 cm. have been analyzed. For all sub-centimeter lesions, minimal invasive staging and treatment approaches must still be considered inappropriate. Less invasive and less extensive treatment methods may be considered in high risk individuals with < or =1 cm. peripheral lesion showing > or =50 ground glass opacity on high resolution CT scan and those with superficial lesion in their central airways without deeper tumor invasion in the bronchial wall. Caution is necessary, however, as clinical staging remains inferior to pathological staging which is based on tissue samples collected after complete tumor removal and mediastinal lymph nodes dissection have been performed.     

Intensified neoadjuvant chemoradiotherapy in locally advanced rectal cancer – impact on long-term quality of life

Aims

In spite of advances in rectal cancer surgery and the use of preoperative 5-fluorouracil-(5-FU) based chemoradiotherapy (CRT) in stage II and III disease distant metastases still occur in about 35–40% of the patients. Intensified preoperative CRT (ICRT) using other drugs in conjunction with 5-FU has been investigated in order to improve the pathological complete remission (pCR) rate and thereby prognosis of patients with locally advanced rectal cancer. However, acute toxicity, especially diarrhea, was reported to be high and no improvement in pCR rates has been observed in randomized trials. Long-term results of these trials are pending. In the present analysis we investigated the impact of ICRT on health related quality of life and long term toxicity.

Methods

The present study included 119 patients with locally advanced rectal cancer who underwent neoadjuvant CRT followed by surgery within controlled clinical trials. Patients received ICRT (n = 83) or standard CRT (n = 36). Evaluation of HRQoL was performed using EORTC QLQ-C30 and QLQ-CR29 questionnaires.

Results

The overall rating of global health status/QLQ scale of the EORTC QLQ-C30 questionnaire was identical in both patient groups but patients in the CRT group showed better results in four out of nine function scales. Concerning symptom scales, patients in the CRT arm exhibited significantly less diarrhea (p = 0.028) and less disorders with taste (0.042).

Conclusions

This data suggests that higher gastrointestinal acute toxicity caused by ICRT might lead to a higher risk of long-term deterioration of “gastrointestinal QoL”. Future results of randomized trials investigating ICRT versus CRT should be discussed in the light of long-term QoL data.     

What are the preoperative predictors of a futile pelvic exenteration in rectal cancers?

IntroductionEarly recurrences and deaths after a morbid procedure like pelvic exenteration are devastating events. The present study aimed at determining the incidence and predictors of futile pelvic exenterations.MethodsConsecutive pelvic exenterations for advanced and recurrent rectal adenocarcinomas operated between January 2013 and January 2021 were included with a minimum of six months follow-up. Futility of exenteration was defined as recurrence or death within six months of operation. Multivariate logistic regression was used to define predictors of futility.ResultsTwo-hundred eighty-five patients were included and 61 patients (21.4%) had a futile resection. Poorly differentiated (or signet) histology, presence of lateral pelvic nodes, M1 disease, and the need for pelvic bone resections predicted a futile resection. The probability of futility was 10%, 20%, 35–40%, 55–60%, and >75% when none, one, two, three, and all four of the predictors were present. The model was able to correctly predict futility in 70% of the cases suggesting moderate discrimination, and showed good calibration.ConclusionsFutile pelvic exenterations were observed in one-fifth of patients. Four strong predictors of futility were identified. The risk of early failures was additive when combination of these adverse features was present, and can be used for patient selection and prognostication.     

Does HIV adversely influence the outcome in advanced non-small-cell lung cancer in the era of HAART?

The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced NSCLC. This suggests that the survival of patients with HIV-related NSCLC may have improved since the introduction of HAART, and this may be due to a decrease in HIV-related deaths.