Correspondence
the size of the centre, indirectly calculated with accrual, was entered as a covariate in the multivariable analysis. In particular, the Cox model reported in our Article1 clearly shows that the prognostic effect of the size of the centre is negligible and not statistically significant; indeed, the estimated hazard ratio of progressionfree survival is better for small centres (0·85). Shimokata and Ando suggest that differences in toxic effects in the standard arms between MITO-71 and the Japanese NOVEL trial4 might be due to the different techniques used for measuring serum creatinine, which might have led to an underestimation of creatinine concentrations in NOVEL and consequent overdosing of carboplatin. We did not collect information on whether creatinine clearance was directly measured or estimated, or which analytical method was used to measure serum creatinine concentrations. We acknowledge the potential implications of the proposed hypothesis. However, this hypothesis does not bias the internal validity of either trial. We declare no competing interests.
*Sandro Pignata, Massimo Di Maio, Ciro Gallo, Francesco Perrone [email protected] Dipartimento di Oncologia Uroginecologia, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale IRCCS, 80131 Napoli, Italy (SP); Unità Sperimentazioni Cliniche, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, IRCCS, Napoli, Italy (MDM, FP); Statistica Medica, Seconda Università di Napoli, Napoli, Italy (CG) 1
2
3
Pignata S, Scambia G, Katsaros D, et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2014; 15: 396–405. Piccart MJ, Bertelsen K, James K, et al. Randomized intergroup trial of cisplatinpaclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 2000; 92: 699–708. du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003; 95: 1320–29.
www.thelancet.com/oncology Vol 15 June 2014
4
Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009; 374: 1331–38.
Rituximab for follicular lymphoma: watch and wait, watch and worry, or watch and live? We read with interest the Article by Kirit Ardeshna1 that compared a watch-and-wait approach versus rituximab in patients with advanced, asymptomatic, follicular lymphoma. This study addresses an important clinical question for patients with an incurable yet often indolent disease—should cancer-directed treatment begin sooner or later if the cancer cannot be cured? Although we applaud the inclusion of patient-reported outcome measures in the study,2 we are concerned about an implicit assertion in the authors’ conclusions, and in the accompanying Comment, namely, that chemotherapy is the solution to psychosocial problems in the cancer clinic. The only differences in patientreported outcomes between the watch-and-wait approach and rituximab treatment in Ardeshna and colleagues’ study1 were for measures of psychological wellbeing, which were higher in the rituximab group. There were otherwise no significant differences in symptom burden, physical functioning, or other key domains of quality of life, nor in survival or rate of disease transformation, and no other key outcome measure were meaningfully different between the groups. With these data, the authors felt that “this finding might be because these patients felt that something active was being done
to combat their lymphoma”. Are they therefore suggesting that cancer-directed therapy should be the primary way to improve patients’ coping and emotional well-being? Is chemotherapy just a more convenient (and often more reimbursable) way of attending to psychosocial needs? We contend that the data from Ardeshna and colleagues’ Article1 tell a very different story: that patients living with an incurable cancer worry about the future and that physicians should be more attuned to this issue as an essential part of providing patientcentred, high-quality, comprehensive cancer care. Instead, little attention is given to how patients and their caregivers can be helped to cope with the uncertainty of an incurable illness. Consequently, lymphoma survivors are known to be at high risk for posttraumatic stress disorder.3 Similar issues are described in patients with chronic lymphocytic leukaemia, who are often told they have so-called good leukaemia, yet they have worse emotional well-being scores compared with patients with other cancers.4 Perhaps if oncologists valued the power of psychosocial care above that of resource-intensive therapies that do not improve outcomes, patients’ experiences of living with cancer could be improved. Rather than to espouse a watch-and-wait strategy, or even—watch-andworry—we should help patients to watch and live. Patients’ difficulties in coping with a chronic cancer diagnosis could be improved by more proven alternatives, such as concurrent palliative and supportive care, psychotherapy, resilience training, physiotherapy, yoga, or other complementary therapies that are provided in many support programmes for cancer patients. In fact, better support with coping skills as delivered by palliative care professionals has been identified as a key factor for how cancer patients might live longer with the e251
Correspondence
e252
addition of palliative care services.5 These and other low-risk, low-cost interventions should be pursued and studied further first, before deciding that chemotherapy is an emotional panacea.
are pending from Genentech and Insys. AA has also had consulting agreements or received honoraria from Bristol Myers Squibb and ACORN Research, and has corporate leadership responsibilities in athenahealth, Advoset, and Orange Leaf Associates.
TLB received a Junior Career Development Award from the National Palliative Care Research Center. AK receives grant support from the Agency for Healthcare Research and Quality, and speaker support from the North Carolina Oncology Society, Association of Community Cancer Centers, American Academy of Hospice and Palliative Medicine, and the American Society of Clinical Oncology. AA has research funding and salary support from the National Institute of Nursing Research, National Cancer Institute, Agency for Healthcare Research and Quality, DARA, GlaxoSmithKline, Celgene, Helsinn, Dendreon, Kanglaite, Bristol Myers Squibb, and Pfizer. Funds
[email protected]
4
Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC 27710, USA (TLB); Center for Learning Health Care, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA (AK, AA)
5
2
3
*Thomas LeBlanc, Arif Kamal, Amy Abernethy
1
LeBlanc TW, Abernethy AP. Quality of life in higher resolution: the next generation of comparative effectiveness research in malignant hematology. Haematologica 2013; 98: 823–24. Smith SK, Zimmerman S, Williams CS, et al. Post-traumatic stress symptoms in long-term non-Hodgkin’s lymphoma survivors: does time heal? J Clin Oncol 2011; 29: 4526–33. Shanafelt TD, Bowen D, Venkat C, et al. Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. Br J Haematol 2007; 139: 255–64. Yoong J, Park ER, Greer JA, et al. Early palliative care in advanced lung cancer: a qualitative study. JAMA Int Med 2013; 173: 283–90.
Ardeshna KM, Qian W, Smith P, et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol 2014; 15: 424–35.
www.thelancet.com/oncology Vol 15 June 2014
the size of the centre, indirectly calculated with accrual, was entered as a covariate in the multivariable analysis. In particular, the Cox model reported in our Article1 clearly shows that the prognostic effect of the size of the centre is negligible and not statistically significant; indeed, the estimated hazard ratio of progressionfree survival is better for small centres (0·85). Shimokata and Ando suggest that differences in toxic effects in the standard arms between MITO-71 and the Japanese NOVEL trial4 might be due to the different techniques used for measuring serum creatinine, which might have led to an underestimation of creatinine concentrations in NOVEL and consequent overdosing of carboplatin. We did not collect information on whether creatinine clearance was directly measured or estimated, or which analytical method was used to measure serum creatinine concentrations. We acknowledge the potential implications of the proposed hypothesis. However, this hypothesis does not bias the internal validity of either trial. We declare no competing interests.
*Sandro Pignata, Massimo Di Maio, Ciro Gallo, Francesco Perrone [email protected] Dipartimento di Oncologia Uroginecologia, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale IRCCS, 80131 Napoli, Italy (SP); Unità Sperimentazioni Cliniche, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, IRCCS, Napoli, Italy (MDM, FP); Statistica Medica, Seconda Università di Napoli, Napoli, Italy (CG) 1
2
3
Pignata S, Scambia G, Katsaros D, et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2014; 15: 396–405. Piccart MJ, Bertelsen K, James K, et al. Randomized intergroup trial of cisplatinpaclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 2000; 92: 699–708. du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003; 95: 1320–29.
www.thelancet.com/oncology Vol 15 June 2014
4
Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009; 374: 1331–38.
Rituximab for follicular lymphoma: watch and wait, watch and worry, or watch and live? We read with interest the Article by Kirit Ardeshna1 that compared a watch-and-wait approach versus rituximab in patients with advanced, asymptomatic, follicular lymphoma. This study addresses an important clinical question for patients with an incurable yet often indolent disease—should cancer-directed treatment begin sooner or later if the cancer cannot be cured? Although we applaud the inclusion of patient-reported outcome measures in the study,2 we are concerned about an implicit assertion in the authors’ conclusions, and in the accompanying Comment, namely, that chemotherapy is the solution to psychosocial problems in the cancer clinic. The only differences in patientreported outcomes between the watch-and-wait approach and rituximab treatment in Ardeshna and colleagues’ study1 were for measures of psychological wellbeing, which were higher in the rituximab group. There were otherwise no significant differences in symptom burden, physical functioning, or other key domains of quality of life, nor in survival or rate of disease transformation, and no other key outcome measure were meaningfully different between the groups. With these data, the authors felt that “this finding might be because these patients felt that something active was being done
to combat their lymphoma”. Are they therefore suggesting that cancer-directed therapy should be the primary way to improve patients’ coping and emotional well-being? Is chemotherapy just a more convenient (and often more reimbursable) way of attending to psychosocial needs? We contend that the data from Ardeshna and colleagues’ Article1 tell a very different story: that patients living with an incurable cancer worry about the future and that physicians should be more attuned to this issue as an essential part of providing patientcentred, high-quality, comprehensive cancer care. Instead, little attention is given to how patients and their caregivers can be helped to cope with the uncertainty of an incurable illness. Consequently, lymphoma survivors are known to be at high risk for posttraumatic stress disorder.3 Similar issues are described in patients with chronic lymphocytic leukaemia, who are often told they have so-called good leukaemia, yet they have worse emotional well-being scores compared with patients with other cancers.4 Perhaps if oncologists valued the power of psychosocial care above that of resource-intensive therapies that do not improve outcomes, patients’ experiences of living with cancer could be improved. Rather than to espouse a watch-and-wait strategy, or even—watch-andworry—we should help patients to watch and live. Patients’ difficulties in coping with a chronic cancer diagnosis could be improved by more proven alternatives, such as concurrent palliative and supportive care, psychotherapy, resilience training, physiotherapy, yoga, or other complementary therapies that are provided in many support programmes for cancer patients. In fact, better support with coping skills as delivered by palliative care professionals has been identified as a key factor for how cancer patients might live longer with the e251
Correspondence
e252
addition of palliative care services.5 These and other low-risk, low-cost interventions should be pursued and studied further first, before deciding that chemotherapy is an emotional panacea.
are pending from Genentech and Insys. AA has also had consulting agreements or received honoraria from Bristol Myers Squibb and ACORN Research, and has corporate leadership responsibilities in athenahealth, Advoset, and Orange Leaf Associates.
TLB received a Junior Career Development Award from the National Palliative Care Research Center. AK receives grant support from the Agency for Healthcare Research and Quality, and speaker support from the North Carolina Oncology Society, Association of Community Cancer Centers, American Academy of Hospice and Palliative Medicine, and the American Society of Clinical Oncology. AA has research funding and salary support from the National Institute of Nursing Research, National Cancer Institute, Agency for Healthcare Research and Quality, DARA, GlaxoSmithKline, Celgene, Helsinn, Dendreon, Kanglaite, Bristol Myers Squibb, and Pfizer. Funds
[email protected]
4
Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC 27710, USA (TLB); Center for Learning Health Care, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA (AK, AA)
5
2
3
*Thomas LeBlanc, Arif Kamal, Amy Abernethy
1
LeBlanc TW, Abernethy AP. Quality of life in higher resolution: the next generation of comparative effectiveness research in malignant hematology. Haematologica 2013; 98: 823–24. Smith SK, Zimmerman S, Williams CS, et al. Post-traumatic stress symptoms in long-term non-Hodgkin’s lymphoma survivors: does time heal? J Clin Oncol 2011; 29: 4526–33. Shanafelt TD, Bowen D, Venkat C, et al. Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. Br J Haematol 2007; 139: 255–64. Yoong J, Park ER, Greer JA, et al. Early palliative care in advanced lung cancer: a qualitative study. JAMA Int Med 2013; 173: 283–90.
Ardeshna KM, Qian W, Smith P, et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol 2014; 15: 424–35.
www.thelancet.com/oncology Vol 15 June 2014
