- Email: [email protected]
AJCC (1997) staging system for nasopharyngeal carcinoma
CORRESPONDENCE
581
Fig. 1 – (a) Computed tomography of large retroperitoneal paraganglioma before treatment; radiotherapy isodose curves are displayed; (b) a 40% reduction in tumour dimensions was noticed 3 months after starting combined radiotherapy and chemotherapy. tumour environment, seem to enhance the activity of radiation. Combined chemo-radiotherapy may lead to a significant reduction of the tumour burden, which renders feasible subsequent surgical removal. M. PITIAKOUDIS M. KOUKOURAKIS A. TSAROUCHA J. MANAVIS A. POLYCHRONIDIS C. SIMOPOULOS
Democritus University of Thrace, Alexandroupolis, Greece
3 Razakaboay M, Maillefert JF, Wendling D, et al. Bone metastases from a paraganglioma. A review of five cases. Rev Rheum Engl Ed 1999;66: 86–91. 4 Mertens WC, Grignon DJ, Romano W. Malignant paraganglioma with skeletal metastases and spinal cord compression: response and palliation with chemotherapy. Clin Oncol 1993;5:126–128. 5 Fitoussi O, Debled M, Masson B, Coindre JM, Kantor G, Bui BN. Brief report: advanced paraganglioma: a role for chemotherapy? Med Pediatr Oncol 1999;33:129–131.
doi:10.1016/j.clon.2004.08.003
References 1 Lack EE, Cubilla AL, Woodruff JM, Lieberman PH. Extra-adrenal paragangliomas of the retroperitoneum. A clinicopathological study of 12 tumors. Am J Surg Pathol 1980;4:109–120. 2 Sclafani LM, Woodruff JM, Brennan MF. Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Surgery 1990;108:1124–1129.
The Question of T2a and N3a in the UICC/AJCC (1997) Staging System for Nasopharyngeal Carcinoma Sir d A. W. M. Lee et al. [1] from the Hong Kong Nasopharyngeal Cancer Study Group in their recent article have questioned the prognostic significance of the current UICC/AJCC (1997) TNM stage assignment for nasopharyngeal carcinoma (NPC). We previously published our data [2] on
582
CLINICAL ONCOLOGY
a cohort of patients with NPC treated with radical radiotherapy alone based on the 1997 TNM staging system. This involved 677 patients who were treated from 1992 to 1994. We updated their survival data and reanalysed the cohort based on the suggested modification by the Hong Kong Group. A total of 760 Singapore citizens with NPC were referred to our department between 1 January 1992 and 31 December 1994. Twelve of them had recurrent NPC, 60 had metastatic disease and 11 had no staging information, and were therefore excluded from the review. A final 677 patients were studied (median age 46.6 years, 72.7% male). The stage distribution using the AJCC/UICC (1997) Staging System was as follows: stage I, 6.1%, IIA, 0.6%, IIB, 38%, III, 17.9%, IVA, 23.6% and IVB, 13.9%. After a median follow-up of 9.2 years (range 7.7–10.8 years), the 5-year overall survival is 58.5%, with actuarial 10-year survival of 45.4%. The 5-year survival by the different stages are 90% stage I, 75% stage IIA, 76% stage IIB, 64% stage III, 36% stage IVA and 29% stage IVB (Fig. 1a). The 5-year overall survival based on T stage was as follows: T1, 78%, T2a, 58%, T2b, 70%, T3, 62%, T4, 32%. A total of 12 patients had T2a and four patients had stage IIA (T2aN0M0) disease. It seems that T2a patients do much worse than T2b patients, but it is difficult to comment with such small numbers in our series. This could be a chance variation, but it could be due to the way we staged our T2a patients, which required the anterior nasal region to be involved (Fig. 2). This group of patients requires further evaluation and may not be in the same prognostic group as T1 patients as suggested.
(a)
1.00
Fig. 2 – Computed tomography PNS showing gross anterior nasal space involvement.
i
(a)
iia
1.0
iib
0.75
n0
0.7
iii
0.50
n1 n2
0.5
iva
n3a
0.25 0.2 ivb
0.00 0
1
2
3
4
5
6
7
8
9
n3b
0.0
10
0
Years from NPC diagnosis
1
2
3
4
5
6
7
8
9
10
9
10
Years from NPC diagnosis
(b) 1.00
I
(b)
1.0
IIB
0.75
N0
0.7 III
N1
0.50 0.5
N2
IVA
0.25 0.2 IVB
0.00 0
1
2
3
4
5
6
7
8
9
10
Years from NPC diagnosis Fig. 1 – (a) Overall survival by stage grouping by 1997 UICC/AJCC staging; (b) overall survival by stage grouping modified according to Hong Kong suggested stage grouping. NPC, nasopharyngeal carcinoma.
N3b
0.0 0
1
2
3
4
5
6
7
8
Years from NPC diagnosis Fig. 3 – (a) Overall survival by N stage by 1997 UICC/AJCC staging; (b) overall survival by N stage modified according to Hong Kong suggested N grouping. NPC, nasopharyngeal carcinoma.
CORRESPONDENCE
As for the N stages, our data showed a 5-year overall survival of N0, 74%, N1, 61%, N2, 51%, N3a, 44% and N3b, 22% (Fig. 3a). There is an overlap of the 95% CI for the overall survival and hazard ratios between N2 and N3a stages, and the difference is not statistically significant. We do concur with the suggestion that N3a and N2 have possibly no significant difference and perhaps should be grouped together as N2 disease. When we regrouped the patients according to the suggestions by the Hong Kong group for the overall stage, the stage distribution was as follows: stage I, 6.7%, stage II, 38.0%, stage III, 20.5%, stage IVA, 25.0% and IVB, 9.9%. The 5-year survival of the different stages are as follows: stage I, 89%, stage II, 76%, stage III, 64%, stage IVA, 34% and stage IVB, 22% (Fig. 1b). It does result in a more even and orderly increase in the hazard ratio for deaths by stage (HRs of 1.7, 3.2, 6.5 and 9.2, respectively). We voice our support for our colleagues in Hong Kong that an improvement in the current UICC/AJCC staging system for NPC is required. We are unable to comment on down-staging of T2a to T1 owing to the small number of patients with T2a disease in our study and the difference in the way we classified patients as having T2 disease. However, we believe that patients with gross anterior nasal involvement (Fig. 3) require further study, as this group of patients may have a worse prognosis and may not be appropriately grouped as T1. We concur that N3a grouping lacks prognostic significance and agree with the suggestion that it be down-staged to N2. We also agree with the overall Stage Groupings that has been suggested. As for other cancer sites, staging systems evolve with clinical results, new discoveries in oncologic sciences and advancements in imaging technologies. In NPC, incorporation of Epstein–Barr virus DNA [3] and other molecular markers into the staging system may not be too far into the future. The current UICC/AJCC staging needs further refinement; it is nonetheless a major achievement in standardising a universally acceptable staging system for NPC. J. S. H. LOW* D. M. K. HENGy J. T. S. WEE*
*Head and Neck Unit, Department of Therapeutic Radiology, National Cancer Centre, Singapore; yClinical Trials and Epidemiology Research Unit, Singapore
583
References 1 Lee AWM, Au JSK, Teo PML, et al. Staging of nasopharyngeal carcinoma: suggestions for improving the current UICC/AJCC staging system. Clin Oncol 2004;16:269–276. 2 Heng DMK, Wee J, Fong KW, et al. Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal cancer. Cancer 1999; 86:1912–1920. 3 Lin JC, Wang WY, Chen KY, et al. Quantification of plasma Epstein–Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 2004;350:2452–2460.
doi:10.1016/j.clon.2004.08.004
Factors Influencing Survival in a Prospective Cohort of Patients with Non-small Cell Lung Cancer: An Updated Assessment Adequate assessment of prognostic factors is essential before deciding what treatment is appropriate for an individual patient with non-small cell lung cancer (NSCLC). Many prognostic factors for survival in NSCLC have been previously described. However, studies reported in the literature are retrospective or derived from selected groups of patients, such as those included in clinical trials [1,2]. Factors influencing survival of patients seen in oncology units, and not enrolled in clinical trials, might differ to published data. In order to study this group of patients, a multicentre study was conducted using a prospective design. Between March 1992 and October 1997, prospective data were collected on 610 consecutive patients attending the Oncology Units of three Regional Hospitals (Girona, Reus, Palma de Mallorca). Inclusion criteria were newly diagnosed NSCLC and Karnofsky performance status (KPS) O 60%. Variables recorded were age, sex, smoking habit ( packs/ year), dyspnoea, chest pain, haemoptysis, cough, superior vena cava syndrome, invasion of mediastinum, KPS, weight loss, albumin, lactate dehydrogenase (LDH), PaO2, PaCO2, pulmonary function tests (FVC, FEV1, FEF25–75), anthropometric measurements, cTNM and histologic subtype. The following treatments were recorded: radical surgery (no macroscopic or microscopic disease) and other surgeries; radical
Fig. 1 – Survival curves according to RECPAM analysis. Only five curves are shown because the three groups with the same median survival are plotted together. Curve A: 24 months (radical surgery); curve B: 14 months (radiation dose R 60 Gy); curve C: 8 months (clinical stage I/II and use of chemotherapy); curve D: 4.5 months (Karnofsky performance status [KPS] ! 60%, clinical stage IIIa/b), and lactate dehydrogenase [LDH] ! 350 IU/L) and curve E: 2.5 months (KPS ! 60% and LDH O 351 IU/L).
581
Fig. 1 – (a) Computed tomography of large retroperitoneal paraganglioma before treatment; radiotherapy isodose curves are displayed; (b) a 40% reduction in tumour dimensions was noticed 3 months after starting combined radiotherapy and chemotherapy. tumour environment, seem to enhance the activity of radiation. Combined chemo-radiotherapy may lead to a significant reduction of the tumour burden, which renders feasible subsequent surgical removal. M. PITIAKOUDIS M. KOUKOURAKIS A. TSAROUCHA J. MANAVIS A. POLYCHRONIDIS C. SIMOPOULOS
Democritus University of Thrace, Alexandroupolis, Greece
3 Razakaboay M, Maillefert JF, Wendling D, et al. Bone metastases from a paraganglioma. A review of five cases. Rev Rheum Engl Ed 1999;66: 86–91. 4 Mertens WC, Grignon DJ, Romano W. Malignant paraganglioma with skeletal metastases and spinal cord compression: response and palliation with chemotherapy. Clin Oncol 1993;5:126–128. 5 Fitoussi O, Debled M, Masson B, Coindre JM, Kantor G, Bui BN. Brief report: advanced paraganglioma: a role for chemotherapy? Med Pediatr Oncol 1999;33:129–131.
doi:10.1016/j.clon.2004.08.003
References 1 Lack EE, Cubilla AL, Woodruff JM, Lieberman PH. Extra-adrenal paragangliomas of the retroperitoneum. A clinicopathological study of 12 tumors. Am J Surg Pathol 1980;4:109–120. 2 Sclafani LM, Woodruff JM, Brennan MF. Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Surgery 1990;108:1124–1129.
The Question of T2a and N3a in the UICC/AJCC (1997) Staging System for Nasopharyngeal Carcinoma Sir d A. W. M. Lee et al. [1] from the Hong Kong Nasopharyngeal Cancer Study Group in their recent article have questioned the prognostic significance of the current UICC/AJCC (1997) TNM stage assignment for nasopharyngeal carcinoma (NPC). We previously published our data [2] on
582
CLINICAL ONCOLOGY
a cohort of patients with NPC treated with radical radiotherapy alone based on the 1997 TNM staging system. This involved 677 patients who were treated from 1992 to 1994. We updated their survival data and reanalysed the cohort based on the suggested modification by the Hong Kong Group. A total of 760 Singapore citizens with NPC were referred to our department between 1 January 1992 and 31 December 1994. Twelve of them had recurrent NPC, 60 had metastatic disease and 11 had no staging information, and were therefore excluded from the review. A final 677 patients were studied (median age 46.6 years, 72.7% male). The stage distribution using the AJCC/UICC (1997) Staging System was as follows: stage I, 6.1%, IIA, 0.6%, IIB, 38%, III, 17.9%, IVA, 23.6% and IVB, 13.9%. After a median follow-up of 9.2 years (range 7.7–10.8 years), the 5-year overall survival is 58.5%, with actuarial 10-year survival of 45.4%. The 5-year survival by the different stages are 90% stage I, 75% stage IIA, 76% stage IIB, 64% stage III, 36% stage IVA and 29% stage IVB (Fig. 1a). The 5-year overall survival based on T stage was as follows: T1, 78%, T2a, 58%, T2b, 70%, T3, 62%, T4, 32%. A total of 12 patients had T2a and four patients had stage IIA (T2aN0M0) disease. It seems that T2a patients do much worse than T2b patients, but it is difficult to comment with such small numbers in our series. This could be a chance variation, but it could be due to the way we staged our T2a patients, which required the anterior nasal region to be involved (Fig. 2). This group of patients requires further evaluation and may not be in the same prognostic group as T1 patients as suggested.
(a)
1.00
Fig. 2 – Computed tomography PNS showing gross anterior nasal space involvement.
i
(a)
iia
1.0
iib
0.75
n0
0.7
iii
0.50
n1 n2
0.5
iva
n3a
0.25 0.2 ivb
0.00 0
1
2
3
4
5
6
7
8
9
n3b
0.0
10
0
Years from NPC diagnosis
1
2
3
4
5
6
7
8
9
10
9
10
Years from NPC diagnosis
(b) 1.00
I
(b)
1.0
IIB
0.75
N0
0.7 III
N1
0.50 0.5
N2
IVA
0.25 0.2 IVB
0.00 0
1
2
3
4
5
6
7
8
9
10
Years from NPC diagnosis Fig. 1 – (a) Overall survival by stage grouping by 1997 UICC/AJCC staging; (b) overall survival by stage grouping modified according to Hong Kong suggested stage grouping. NPC, nasopharyngeal carcinoma.
N3b
0.0 0
1
2
3
4
5
6
7
8
Years from NPC diagnosis Fig. 3 – (a) Overall survival by N stage by 1997 UICC/AJCC staging; (b) overall survival by N stage modified according to Hong Kong suggested N grouping. NPC, nasopharyngeal carcinoma.
CORRESPONDENCE
As for the N stages, our data showed a 5-year overall survival of N0, 74%, N1, 61%, N2, 51%, N3a, 44% and N3b, 22% (Fig. 3a). There is an overlap of the 95% CI for the overall survival and hazard ratios between N2 and N3a stages, and the difference is not statistically significant. We do concur with the suggestion that N3a and N2 have possibly no significant difference and perhaps should be grouped together as N2 disease. When we regrouped the patients according to the suggestions by the Hong Kong group for the overall stage, the stage distribution was as follows: stage I, 6.7%, stage II, 38.0%, stage III, 20.5%, stage IVA, 25.0% and IVB, 9.9%. The 5-year survival of the different stages are as follows: stage I, 89%, stage II, 76%, stage III, 64%, stage IVA, 34% and stage IVB, 22% (Fig. 1b). It does result in a more even and orderly increase in the hazard ratio for deaths by stage (HRs of 1.7, 3.2, 6.5 and 9.2, respectively). We voice our support for our colleagues in Hong Kong that an improvement in the current UICC/AJCC staging system for NPC is required. We are unable to comment on down-staging of T2a to T1 owing to the small number of patients with T2a disease in our study and the difference in the way we classified patients as having T2 disease. However, we believe that patients with gross anterior nasal involvement (Fig. 3) require further study, as this group of patients may have a worse prognosis and may not be appropriately grouped as T1. We concur that N3a grouping lacks prognostic significance and agree with the suggestion that it be down-staged to N2. We also agree with the overall Stage Groupings that has been suggested. As for other cancer sites, staging systems evolve with clinical results, new discoveries in oncologic sciences and advancements in imaging technologies. In NPC, incorporation of Epstein–Barr virus DNA [3] and other molecular markers into the staging system may not be too far into the future. The current UICC/AJCC staging needs further refinement; it is nonetheless a major achievement in standardising a universally acceptable staging system for NPC. J. S. H. LOW* D. M. K. HENGy J. T. S. WEE*
*Head and Neck Unit, Department of Therapeutic Radiology, National Cancer Centre, Singapore; yClinical Trials and Epidemiology Research Unit, Singapore
583
References 1 Lee AWM, Au JSK, Teo PML, et al. Staging of nasopharyngeal carcinoma: suggestions for improving the current UICC/AJCC staging system. Clin Oncol 2004;16:269–276. 2 Heng DMK, Wee J, Fong KW, et al. Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal cancer. Cancer 1999; 86:1912–1920. 3 Lin JC, Wang WY, Chen KY, et al. Quantification of plasma Epstein–Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 2004;350:2452–2460.
doi:10.1016/j.clon.2004.08.004
Factors Influencing Survival in a Prospective Cohort of Patients with Non-small Cell Lung Cancer: An Updated Assessment Adequate assessment of prognostic factors is essential before deciding what treatment is appropriate for an individual patient with non-small cell lung cancer (NSCLC). Many prognostic factors for survival in NSCLC have been previously described. However, studies reported in the literature are retrospective or derived from selected groups of patients, such as those included in clinical trials [1,2]. Factors influencing survival of patients seen in oncology units, and not enrolled in clinical trials, might differ to published data. In order to study this group of patients, a multicentre study was conducted using a prospective design. Between March 1992 and October 1997, prospective data were collected on 610 consecutive patients attending the Oncology Units of three Regional Hospitals (Girona, Reus, Palma de Mallorca). Inclusion criteria were newly diagnosed NSCLC and Karnofsky performance status (KPS) O 60%. Variables recorded were age, sex, smoking habit ( packs/ year), dyspnoea, chest pain, haemoptysis, cough, superior vena cava syndrome, invasion of mediastinum, KPS, weight loss, albumin, lactate dehydrogenase (LDH), PaO2, PaCO2, pulmonary function tests (FVC, FEV1, FEF25–75), anthropometric measurements, cTNM and histologic subtype. The following treatments were recorded: radical surgery (no macroscopic or microscopic disease) and other surgeries; radical
Fig. 1 – Survival curves according to RECPAM analysis. Only five curves are shown because the three groups with the same median survival are plotted together. Curve A: 24 months (radical surgery); curve B: 14 months (radiation dose R 60 Gy); curve C: 8 months (clinical stage I/II and use of chemotherapy); curve D: 4.5 months (Karnofsky performance status [KPS] ! 60%, clinical stage IIIa/b), and lactate dehydrogenase [LDH] ! 350 IU/L) and curve E: 2.5 months (KPS ! 60% and LDH O 351 IU/L).