- Email: [email protected]
Altered fractionated radiotherapy in head and neck cancer
Correspondence
We declare that we have no conflict of interest.
*Hajo Grundmann, Edine Tiemersma [email protected] Centre for Infectious Diseases Epidemiology, National Institute for Public Health and the Environment, Bilthoven 3720BA, Netherlands 1
2
3
Orrett FA, Land M. Methicillin-resistant Staphylococcus aureus prevalence: current susceptibility patterns in Trinidad. BMC Infect Dis 2006; 6: 83. Asghar AH, Momenah AM. Methicillin resistance among Staphylococcus aureus isolates from Saudi hospitals. Med Princ Pract 2006; 15: 52–55. Cornaglia G, Hryniewicz W, Jarlier V, et al. European recommendations for antimicrobial resistance surveillance. Clin Microbiol Infect 2004; 10: 349–83.
Altered fractionated radiotherapy in head and neck cancer We believe that a few important observations are worth considering when interpreting the results of the MARCH meta-analysis of hyperfractionated or accelerated radiotherapy in head and neck cancer (Sept 2, p 843).1 First, patients with stage I–II cancers, who comprised 26% of the www.thelancet.com Vol 368 November 25, 2006
total, benefited minimally from altered fractionation (hazard ratio close to unity). The greatest benefit was for those with stage III, for whom the relative risk of death was reduced by more than 20%. Hence, to generalise the benefit of altered fractionation across all stages might not be entirely correct. Second, age and performance status had a substantial effect on outcome in patients younger than 50 years, with good performance status deriving maximum benefit from altered fractionation. However, this group of patients can also tolerate aggressive chemoradiotherapy, and in view of the comparable benefits,1,2 whether it is best to offer them chemoradiation or altered fractionation remains unclear. The only published trial3 to compare the two showed no clear benefit of one over the other. There is also a case for cost-benefit analysis, particularly in resource-limited settings. In this context we are trying to explore the possibility of an indirect comparison between the two approaches from the respective meta-analyses. Finally, altered fractionation was more efficient in reducing local failures (hazard ratio 0·77, p<0·001), than nodal failures (0·87, p<0·01), as also seen in the MACH-NC analysis.2 Biological factors such as clonogen density, hypoxic fraction, labelling index, potential doubling time, and survival fraction at 2 Gy affect radiocurability. Since large nodes are likely to harbour more radioresistant clones, radiobiological modelling should also include nodal tissues rather than being restricted to primary tumour. We declare that we have no conflict of interest.
C Srinivas, J P Agarwal, *S Ghosh Laskar, T Gupta, K A Dinshaw [email protected] Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra 400012, India 1
Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368: 843–54.
2
3
Bourhis J, Amand C, Pignon JP, on behalf of the MACH-NC collaborative group. Update of MACH-NC (Meta-analysis of Chemotherapy in Head and Neck Cancer) database focused on concomitant chemo-radiotherapy. Proc Am Soc Clin Oncol 2004; 22: 488s (abstr 5505). Olmi P, Crispino S, Fallai C, et al. Locoregionally advanced carcinoma of oropharynx: conventional radiotherapy versus hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy: a multicenter randomized trial. Int J Radiat Biol Phys 2003; 55: 78–92.
Jean Bourhis and colleagues1 found that altered fractionated radiotherapy had a significant benefit over conventional radiotherapy in terms of survival and locoregional and local control in patients with head and neck cancer. Since chemoradiotherapy for cancer involves high toxicity, the balance between treatment effects and treatment-related toxic effects is a concern. Treatment schedules are frequently determined on the basis of patients’ backgrounds, including their age and comorbidities. Bourhis and colleagues showed that altered fractionated radiotherapy was associated with a significantly better overall survival in the analysis involving the whole patient population; however, its benefits differed significantly according to the patients’ age. In patients who were 50 years or younger, altered fractionated radiotherapy was associated with a 45·6% reduction in the hazard ratio of death, whereas its effects were marginal in patients between 51 and 70 years; patients given altered fractionated radiotherapy who were 71 years or older tended to have a poor prognosis compared with those given conventional radiotherapy. These findings suggest that altered fractionated radiotherapy causes substantial toxic effects in elderly patients, impairing their prognosis. The median age of patients with head and neck cancer is about 70 years in the USA,2,3 and patients who are 50 years or younger represent a minority population. We would be grateful if Bourhis and
The printed journal includes an image merely for illustration
e-mail submissions to [email protected]
1867
Science Photo Library
network for Antimicrobial Resistance in the Mediterranean Region (ARMed) that were available at the time of submission. It is therefore not unexpected that our map represents a conservative, yet defendable, estimate of the MRSA situation in late 2005. Because the EARSS data 2005 and the latest prevalence studies for Trinidad1 and Saudi Arabia2 were not published at the time of submission, we welcome the update provided by Heiman Wertheim and Henri Verbrugh, but caution against the indiscriminate use of data from all available sources. The current debate indicates the need for a set of generally accepted and agreed on criteria for communicating and comparing surveillance data for antimicrobial resistance worldwide, ideally according to rules proposed by international guidelines3 or already used by multinational surveillance networks such as EARSS.
Correspondence
colleagues could provide the results of the analysis focused on elderly patients. We declare that we have no conflict of interest. Full documentation on the nutrition support guidelines can be obtained at http://www. rcseng.ac.uk/publications/docs/ nutrition_support_guidelines. html
Morihito Takita, Tomoko Matsumura, Yuko Kodama, Yuji Tanaka, *Masahiro Kami [email protected] Division of Exploratory Research, Institute of Medical Science, University of Tokyo, 4-6-1, Shiroganedai, Minato-ku 180-8639, Tokyo, Japan 1
2
3
Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368: 843–54. National Cancer Institute. Age-specific (crude) SEER incidence rates by ‘expanded’ race for larynx cancer, both sexes, SEER 13 registries for 1994–2003. http://seer.cancer.gov/faststats/ sites.php?stat=Incidence&site=Larynx+Cancer &x=13&y=16 (accessed Sept 6, 2006). National Cancer Institute. Age-specific (crude) SEER incidence rates by ‘expanded’ race for oral cavity and pharynx cancer, both sexes, SEER 13 registries for 1994–2003. http://seer.cancer.gov/faststats/sites.php?sta t=Incidence&site=Oral+Cavity+and+Pharynx +Cancer&x=7&y=15 (accessed Sept 6, 2006).
cancer (MACH-NC).1,2 An effect of chemotherapy was seen for death related to head and neck cancer in MACH-NC independently of age. In both cases, the competing risk of death from other alcohol-related and tobaccorelated diseases is likely to have a major role. The proportion of deaths not due to head and neck cancer increased with age, from 18% at age 50 years or younger to 41% at age 71 years or older in MARCH, and from 15% to 39%, respectively, in MACH-NC.2 We declare that we have no conflict of interest.
*Jean-Pierre Pignon, Aurélie Le Maître, Richard Sylvester, Jean Bourhis [email protected] Service de Biostatistique et d’Epidémiologie (J-PP, ALM) and Département de Radiothérapie (JB), Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France; and European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium (RS). 1
Authors’ reply
e-mail submissions to [email protected]
1868
We agree with C Srinivas and colleagues that it is difficult to extrapolate the results of the Meta-Analysis of Radiotherapy in Carcinoma of Head and Neck (MARCH) to stage I and II, because 99% of stage I and 58% of stage II patients were included in the group given accelerated fractionation without total dose reduction. This group represents 54% of the MARCH population (see webtable 4 of original report). The absence of benefit after 70 years of age in MARCH, both for overall survival and for death related to head and neck cancer, is an indirect argument in favour of a possible increase in toxic effects in this population, as suggested by Morihito Takita and colleagues. Another explanation could be worse compliance than in younger patients, related or not to acute toxic effects. An absence of benefit on overall survival after 70 years was seen both for altered fractionated radiotherapy (MARCH) and chemotherapy concomitant to radiotherapy in the Meta-Analysis of Chemotherapy in Head and Neck
2
Bourhis J, Amand C, Pignon JP, on behalf of the MACH-NC Collaborative Group. Update of MACH-NC (Meta-Analysis of Chemotherapy in Head & Neck Cancer) database focused on concomitant chemoradiotherapy. Proc Am Soc Clin Oncol 2004; 22: 488. Bourhis J, Le Maître A, Pignon J, et al, on behalf of the MACH-NC MARCH Groups. Impact of age on treatment effect in locally advanced head and neck cancer (HNC): two individual patient data meta-analyses. Proc Am Soc Clin Oncol 2006; 24: 280s.
Parenteral nutrition in adults with a functional gastrointestinal tract Contrary to the title, parenteral nutrition is for when nutrition cannot be safely delivered into the gastrointestinal tract. Gary Zaloga (April 1, p 1101)1 points out that for most patients this is not the case. I suggest that his Review has a perspective that reflects his home country, where parenteral nutrition is overused, and that it is its misuse that is the problem rather than parenteral nutrition per se. Decision-making in nutrition support requires recognition of the malnourished or soon to be and follows an escalating pathway of care from oral food to enteral nutrition and
only finally to parenteral nutrition if needed. In response to Zaloga’s concluding paragraph about the need to develop evidence-based guidelines, the UK’s National Institute for Health and Clinical Excellence (NICE) has just published some.2 The working group that developed these guidelines recognised the fallacy of studies that have compared parenteral nutrition with enteral nutrition since only patients assured to have a functional gastrointestinal tract are recruited. Furthermore, the considerable change in the practice, nature, and content of parenteral nutrition has meant that historical studies have perhaps little to contribute to this debate. I was a member of the National Collaborating Centre for Acute Care working group that developed the guidelines for NICE, but these are my own personal views. I have received lecture honoraria from several nutrition companies over the years but have no direct commercial association or connections.
Richard D Griffiths [email protected] Division of Metabolic and Cellular Medicine, School of Clinical Science, University of Liverpool, Liverpool L69 3GA, UK 1
2
Zaloga GP. Parenteral nutrition in adult inpatients with functioning gastrointestinal tracts: assessment of outcomes. Lancet 2006; 367: 1101–11. National Institute for Health and Clinical Excellence. Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. Clinical guideline no 32. London: NICE, 2006: http://www.nice.org.uk/ CG032 (accessed Oct 23, 2006).
Will the new WHO growth references do more harm than good? Exclusive breastfeeding for 6 months is the normal way to feed all infants. The new WHO growth reference released in April, 2006, is based on breastfed infants under optimum conditions.1 The sample is highly selected for the factors likely to promote growth in breastfed infants, and less than 10% of those initially surveyed were included in the final study. www.thelancet.com Vol 368 November 25, 2006
We declare that we have no conflict of interest.
*Hajo Grundmann, Edine Tiemersma [email protected] Centre for Infectious Diseases Epidemiology, National Institute for Public Health and the Environment, Bilthoven 3720BA, Netherlands 1
2
3
Orrett FA, Land M. Methicillin-resistant Staphylococcus aureus prevalence: current susceptibility patterns in Trinidad. BMC Infect Dis 2006; 6: 83. Asghar AH, Momenah AM. Methicillin resistance among Staphylococcus aureus isolates from Saudi hospitals. Med Princ Pract 2006; 15: 52–55. Cornaglia G, Hryniewicz W, Jarlier V, et al. European recommendations for antimicrobial resistance surveillance. Clin Microbiol Infect 2004; 10: 349–83.
Altered fractionated radiotherapy in head and neck cancer We believe that a few important observations are worth considering when interpreting the results of the MARCH meta-analysis of hyperfractionated or accelerated radiotherapy in head and neck cancer (Sept 2, p 843).1 First, patients with stage I–II cancers, who comprised 26% of the www.thelancet.com Vol 368 November 25, 2006
total, benefited minimally from altered fractionation (hazard ratio close to unity). The greatest benefit was for those with stage III, for whom the relative risk of death was reduced by more than 20%. Hence, to generalise the benefit of altered fractionation across all stages might not be entirely correct. Second, age and performance status had a substantial effect on outcome in patients younger than 50 years, with good performance status deriving maximum benefit from altered fractionation. However, this group of patients can also tolerate aggressive chemoradiotherapy, and in view of the comparable benefits,1,2 whether it is best to offer them chemoradiation or altered fractionation remains unclear. The only published trial3 to compare the two showed no clear benefit of one over the other. There is also a case for cost-benefit analysis, particularly in resource-limited settings. In this context we are trying to explore the possibility of an indirect comparison between the two approaches from the respective meta-analyses. Finally, altered fractionation was more efficient in reducing local failures (hazard ratio 0·77, p<0·001), than nodal failures (0·87, p<0·01), as also seen in the MACH-NC analysis.2 Biological factors such as clonogen density, hypoxic fraction, labelling index, potential doubling time, and survival fraction at 2 Gy affect radiocurability. Since large nodes are likely to harbour more radioresistant clones, radiobiological modelling should also include nodal tissues rather than being restricted to primary tumour. We declare that we have no conflict of interest.
C Srinivas, J P Agarwal, *S Ghosh Laskar, T Gupta, K A Dinshaw [email protected] Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra 400012, India 1
Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368: 843–54.
2
3
Bourhis J, Amand C, Pignon JP, on behalf of the MACH-NC collaborative group. Update of MACH-NC (Meta-analysis of Chemotherapy in Head and Neck Cancer) database focused on concomitant chemo-radiotherapy. Proc Am Soc Clin Oncol 2004; 22: 488s (abstr 5505). Olmi P, Crispino S, Fallai C, et al. Locoregionally advanced carcinoma of oropharynx: conventional radiotherapy versus hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy: a multicenter randomized trial. Int J Radiat Biol Phys 2003; 55: 78–92.
Jean Bourhis and colleagues1 found that altered fractionated radiotherapy had a significant benefit over conventional radiotherapy in terms of survival and locoregional and local control in patients with head and neck cancer. Since chemoradiotherapy for cancer involves high toxicity, the balance between treatment effects and treatment-related toxic effects is a concern. Treatment schedules are frequently determined on the basis of patients’ backgrounds, including their age and comorbidities. Bourhis and colleagues showed that altered fractionated radiotherapy was associated with a significantly better overall survival in the analysis involving the whole patient population; however, its benefits differed significantly according to the patients’ age. In patients who were 50 years or younger, altered fractionated radiotherapy was associated with a 45·6% reduction in the hazard ratio of death, whereas its effects were marginal in patients between 51 and 70 years; patients given altered fractionated radiotherapy who were 71 years or older tended to have a poor prognosis compared with those given conventional radiotherapy. These findings suggest that altered fractionated radiotherapy causes substantial toxic effects in elderly patients, impairing their prognosis. The median age of patients with head and neck cancer is about 70 years in the USA,2,3 and patients who are 50 years or younger represent a minority population. We would be grateful if Bourhis and
The printed journal includes an image merely for illustration
e-mail submissions to [email protected]
1867
Science Photo Library
network for Antimicrobial Resistance in the Mediterranean Region (ARMed) that were available at the time of submission. It is therefore not unexpected that our map represents a conservative, yet defendable, estimate of the MRSA situation in late 2005. Because the EARSS data 2005 and the latest prevalence studies for Trinidad1 and Saudi Arabia2 were not published at the time of submission, we welcome the update provided by Heiman Wertheim and Henri Verbrugh, but caution against the indiscriminate use of data from all available sources. The current debate indicates the need for a set of generally accepted and agreed on criteria for communicating and comparing surveillance data for antimicrobial resistance worldwide, ideally according to rules proposed by international guidelines3 or already used by multinational surveillance networks such as EARSS.
Correspondence
colleagues could provide the results of the analysis focused on elderly patients. We declare that we have no conflict of interest. Full documentation on the nutrition support guidelines can be obtained at http://www. rcseng.ac.uk/publications/docs/ nutrition_support_guidelines. html
Morihito Takita, Tomoko Matsumura, Yuko Kodama, Yuji Tanaka, *Masahiro Kami [email protected] Division of Exploratory Research, Institute of Medical Science, University of Tokyo, 4-6-1, Shiroganedai, Minato-ku 180-8639, Tokyo, Japan 1
2
3
Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368: 843–54. National Cancer Institute. Age-specific (crude) SEER incidence rates by ‘expanded’ race for larynx cancer, both sexes, SEER 13 registries for 1994–2003. http://seer.cancer.gov/faststats/ sites.php?stat=Incidence&site=Larynx+Cancer &x=13&y=16 (accessed Sept 6, 2006). National Cancer Institute. Age-specific (crude) SEER incidence rates by ‘expanded’ race for oral cavity and pharynx cancer, both sexes, SEER 13 registries for 1994–2003. http://seer.cancer.gov/faststats/sites.php?sta t=Incidence&site=Oral+Cavity+and+Pharynx +Cancer&x=7&y=15 (accessed Sept 6, 2006).
cancer (MACH-NC).1,2 An effect of chemotherapy was seen for death related to head and neck cancer in MACH-NC independently of age. In both cases, the competing risk of death from other alcohol-related and tobaccorelated diseases is likely to have a major role. The proportion of deaths not due to head and neck cancer increased with age, from 18% at age 50 years or younger to 41% at age 71 years or older in MARCH, and from 15% to 39%, respectively, in MACH-NC.2 We declare that we have no conflict of interest.
*Jean-Pierre Pignon, Aurélie Le Maître, Richard Sylvester, Jean Bourhis [email protected] Service de Biostatistique et d’Epidémiologie (J-PP, ALM) and Département de Radiothérapie (JB), Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France; and European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium (RS). 1
Authors’ reply
e-mail submissions to [email protected]
1868
We agree with C Srinivas and colleagues that it is difficult to extrapolate the results of the Meta-Analysis of Radiotherapy in Carcinoma of Head and Neck (MARCH) to stage I and II, because 99% of stage I and 58% of stage II patients were included in the group given accelerated fractionation without total dose reduction. This group represents 54% of the MARCH population (see webtable 4 of original report). The absence of benefit after 70 years of age in MARCH, both for overall survival and for death related to head and neck cancer, is an indirect argument in favour of a possible increase in toxic effects in this population, as suggested by Morihito Takita and colleagues. Another explanation could be worse compliance than in younger patients, related or not to acute toxic effects. An absence of benefit on overall survival after 70 years was seen both for altered fractionated radiotherapy (MARCH) and chemotherapy concomitant to radiotherapy in the Meta-Analysis of Chemotherapy in Head and Neck
2
Bourhis J, Amand C, Pignon JP, on behalf of the MACH-NC Collaborative Group. Update of MACH-NC (Meta-Analysis of Chemotherapy in Head & Neck Cancer) database focused on concomitant chemoradiotherapy. Proc Am Soc Clin Oncol 2004; 22: 488. Bourhis J, Le Maître A, Pignon J, et al, on behalf of the MACH-NC MARCH Groups. Impact of age on treatment effect in locally advanced head and neck cancer (HNC): two individual patient data meta-analyses. Proc Am Soc Clin Oncol 2006; 24: 280s.
Parenteral nutrition in adults with a functional gastrointestinal tract Contrary to the title, parenteral nutrition is for when nutrition cannot be safely delivered into the gastrointestinal tract. Gary Zaloga (April 1, p 1101)1 points out that for most patients this is not the case. I suggest that his Review has a perspective that reflects his home country, where parenteral nutrition is overused, and that it is its misuse that is the problem rather than parenteral nutrition per se. Decision-making in nutrition support requires recognition of the malnourished or soon to be and follows an escalating pathway of care from oral food to enteral nutrition and
only finally to parenteral nutrition if needed. In response to Zaloga’s concluding paragraph about the need to develop evidence-based guidelines, the UK’s National Institute for Health and Clinical Excellence (NICE) has just published some.2 The working group that developed these guidelines recognised the fallacy of studies that have compared parenteral nutrition with enteral nutrition since only patients assured to have a functional gastrointestinal tract are recruited. Furthermore, the considerable change in the practice, nature, and content of parenteral nutrition has meant that historical studies have perhaps little to contribute to this debate. I was a member of the National Collaborating Centre for Acute Care working group that developed the guidelines for NICE, but these are my own personal views. I have received lecture honoraria from several nutrition companies over the years but have no direct commercial association or connections.
Richard D Griffiths [email protected] Division of Metabolic and Cellular Medicine, School of Clinical Science, University of Liverpool, Liverpool L69 3GA, UK 1
2
Zaloga GP. Parenteral nutrition in adult inpatients with functioning gastrointestinal tracts: assessment of outcomes. Lancet 2006; 367: 1101–11. National Institute for Health and Clinical Excellence. Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. Clinical guideline no 32. London: NICE, 2006: http://www.nice.org.uk/ CG032 (accessed Oct 23, 2006).
Will the new WHO growth references do more harm than good? Exclusive breastfeeding for 6 months is the normal way to feed all infants. The new WHO growth reference released in April, 2006, is based on breastfed infants under optimum conditions.1 The sample is highly selected for the factors likely to promote growth in breastfed infants, and less than 10% of those initially surveyed were included in the final study. www.thelancet.com Vol 368 November 25, 2006