A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion

Georgia M. Beasley, Ketan Sharma, Joyce Wong, Mike Miller, Ryan S. Turley, Michael Lidsky, Melanie Masoud, Mark W. Dewhirst, Paul J. Mosca, Jonathan S. Zager, Douglas Tyler

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P <.001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P <.001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P <.001) and the mean pH at 30 minutes (7.06 vs 7.15; P <.001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P =.03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P =.005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

Original languageEnglish (US)
Pages (from-to)6136-6143
Number of pages8
JournalCancer
Volume118
Issue number24
DOIs
StatePublished - Dec 15 2012
Externally publishedYes

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Melphalan
Upper Extremity
Lower Extremity
Extremities
Sarcoma
Melanoma
Merkel Cells
Confidence Intervals
Blood Gas Analysis
Poisons
Squamous Cell Carcinoma

Keywords

  • in-transit disease
  • limb infusion
  • melanoma
  • melphalan
  • tumor hypoxia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion. / Beasley, Georgia M.; Sharma, Ketan; Wong, Joyce; Miller, Mike; Turley, Ryan S.; Lidsky, Michael; Masoud, Melanie; Dewhirst, Mark W.; Mosca, Paul J.; Zager, Jonathan S.; Tyler, Douglas.

In: Cancer, Vol. 118, No. 24, 15.12.2012, p. 6136-6143.

Research output: Contribution to journalArticle

Beasley, GM, Sharma, K, Wong, J, Miller, M, Turley, RS, Lidsky, M, Masoud, M, Dewhirst, MW, Mosca, PJ, Zager, JS & Tyler, D 2012, 'A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion', Cancer, vol. 118, no. 24, pp. 6136-6143. https://doi.org/10.1002/cncr.27676
Beasley, Georgia M. ; Sharma, Ketan ; Wong, Joyce ; Miller, Mike ; Turley, Ryan S. ; Lidsky, Michael ; Masoud, Melanie ; Dewhirst, Mark W. ; Mosca, Paul J. ; Zager, Jonathan S. ; Tyler, Douglas. / A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion. In: Cancer. 2012 ; Vol. 118, No. 24. pp. 6136-6143.
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abstract = "BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77{\%}); sarcoma, 5 of 47 patients (11{\%}); Merkel cell sarcoma, 3 of 47 patients (6{\%}), and squamous cell carcinoma, 3 of 47 patients (6{\%}). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P <.001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P <.001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P <.001) and the mean pH at 30 minutes (7.06 vs 7.15; P <.001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P =.03). The rate of regional toxicity grade ≥3 for UE ILI was 7{\%} compared with 24{\%} (P =.005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28{\%}; 95{\%} confidence interval, 16{\%}-44{\%}) compared with LE ILI procedures (32{\%}; 95{\%} confidence interval, 25{\%}-39{\%}). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.",
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author = "Beasley, {Georgia M.} and Ketan Sharma and Joyce Wong and Mike Miller and Turley, {Ryan S.} and Michael Lidsky and Melanie Masoud and Dewhirst, {Mark W.} and Mosca, {Paul J.} and Zager, {Jonathan S.} and Douglas Tyler",
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AU - Beasley, Georgia M.

AU - Sharma, Ketan

AU - Wong, Joyce

AU - Miller, Mike

AU - Turley, Ryan S.

AU - Lidsky, Michael

AU - Masoud, Melanie

AU - Dewhirst, Mark W.

AU - Mosca, Paul J.

AU - Zager, Jonathan S.

AU - Tyler, Douglas

PY - 2012/12/15

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N2 - BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P <.001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P <.001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P <.001) and the mean pH at 30 minutes (7.06 vs 7.15; P <.001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P =.03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P =.005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

AB - BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P <.001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P <.001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P <.001) and the mean pH at 30 minutes (7.06 vs 7.15; P <.001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P =.03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P =.005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

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KW - tumor hypoxia

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