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Journal articles on the topic 'Dose intensity'

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Published: 9 March 2023

Last updated: 10 March 2023

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1

Ozols, R. F., J. T. Thigpen, J. Dauplat, N. Colombo, M. J. Piccart, K. Bertelsen, L. Levin, and B. Lund. "Dose intensity." Annals of Oncology 4 (1993): S49—S56. http://dx.doi.org/10.1093/annonc/4.suppl_4.s49.

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2

SURBONE, ANTONELLA, and VINCENT T. DeVITA. "Dose Intensity." Annals of the New York Academy of Sciences 698, no. 1 Breast Cancer (November 1993): 279–88. http://dx.doi.org/10.1111/j.1749-6632.1993.tb17219.x.

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3

Coldman, A. J., and C. M. Coppin. "Calculating dose intensity." Journal of Clinical Oncology 9, no. 9 (September 1991): 1713–14. http://dx.doi.org/10.1200/jco.1991.9.9.1713.

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4

Piccart, M. J., L. Biganzoli, and A. Di Leo. "S34 Dose intensity and dose density." European Journal of Cancer 34 (February 1998): S8. http://dx.doi.org/10.1016/s0959-8049(97)89207-6.

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5

Portlock, C. S. "Dose density and dose intensity: where does CHOP go from here?" Annals of Oncology 13, no. 9 (September 2002): 1329–30. http://dx.doi.org/10.1093/annonc/mdf238.

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6

Tonkin, Katia, and Ian Tannock. "Dose Intensity in Chemotherapy." Journal of Clinical Oncology 3, no. 6 (June 1985): 891. http://dx.doi.org/10.1200/jco.1985.3.6.891.

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To the Editor: In a recent article, Hryniuk and Bush have established a strong correlation between dose intensity of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy, and the rate of tumor response in patients with metastatic breast cancer. They also observed a significant correlation between rate of tumor response and median survival time (r = .66, P < .001). The authors were careful to avoid the conclusion that there was a direct correlation between dose intensity and median survival, but it is surprising that they did not examine this more important relationship directly. We have used data provided in their paper to test for correlation between median survival time and dose intensity for patients receiving CMF chemotherapy, and find little evidence for a direct relationship (r = .25, P = .27—two-tailed Student's t test). Moreover, if the studies are weighted according to the number of patients in them, the correlation coefficient is even lower (r = .14, P = .50—two-tailed Student's t test). Unfortunately, metastatic breast cancer is not cured by chemotherapy, and appropriate endpoints are those of palliation, namely quantity and quality of survival. Quality of survival cannot easily be addressed in a retrospective review, but increasing dose intensity has the capability both to improve quality of life by ameliorating symptoms of disease, and to decrease it by adding toxicity. Factors such as sites of metastases and performance status of patients are known to influence duration of survival and could mask a relationship with dose intensity. However, the data reviewed by Hryniuk and Bush do not provide evidence for a relationship between dose of chemotherapy and survival. A prospective randomized trial is in progress at our institution that addresses the relationship between dose intensity of CMF chemotherapy and both quantity and quality of survival for patients with metastatic breast cancer. In the absence of results from this and other prospective trials that address the dose-response effect of chemotherapy in palliation, one should not assume that more is better.

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7

Hryniak, William. "Dose Intensity…and Beyond." Cancer Investigation 22, no. 4 (January 2004): 648–49. http://dx.doi.org/10.1081/cnv-200027172.

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8

Meyer, R., M. Goodyear, and W. Hryniuk. "Dose intensity and lymphoma." Journal of Clinical Oncology 9, no. 8 (August 1991): 1511. http://dx.doi.org/10.1200/jco.1991.9.8.1511.

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9

Coldman, Andrew J., Christopher M. L. Coppin, and James H. Goldie. "Models for dose intensity." Mathematical Biosciences 92, no. 1 (November 1988): 97–113. http://dx.doi.org/10.1016/0025-5564(88)90007-7.

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10

Gianni, A. M., and M. J. Piccart. "Optimising chemotherapy dose density and dose intensity." European Journal of Cancer 36 (April 2000): 1–3. http://dx.doi.org/10.1016/s0959-8049(99)00258-0.

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11

Dodwell, DJ, H. Gurney, and N. Thatcher. "Dose intensity in cancer chemotherapy." British Journal of Cancer 61, no. 6 (June 1990): 789–94. http://dx.doi.org/10.1038/bjc.1990.178.

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12

Cavaletti, G., L. Marzorati, G. Bogliun, N. Colombo, M. Marzola, M. R. Pittelli, and G. Tredici. "Cisplatin-lnduced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity." Cancer 69, no. 1 (January 1, 1992): 203–7. http://dx.doi.org/10.1002/1097-0142(19920101)69:1<203::aid-cncr2820690133>3.0.co;2-1.

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13

Warde, Nick. "Does the dose intensity of BEP chemotherapy affect survival?" Nature Reviews Urology 7, no. 9 (September 2010): 477. http://dx.doi.org/10.1038/nrurol.2010.127.

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14

Costabel, U., SD Nathan, L. Lancaster, C. Albera, MK Glassberg, JJ Swigris, F. Gilberg, KU Kirchgaessler, U. Petzinger, and PW Noble. "Dose modifications and dose intensity during treatment with pirfenidone." Pneumologie 71, S 01 (February 23, 2017): S1—S125. http://dx.doi.org/10.1055/s-0037-1598499.

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15

Livingston, Robert B. "Dose intensity and high dose therapy. Two different concepts." Cancer 74, S3 (August 1, 1994): 1177–83. http://dx.doi.org/10.1002/1097-0142(19940801)74:3+<1177::aid-cncr2820741529>3.0.co;2-7.

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16

Winkelman, Chris, Abdus Sattar, Hasina Momotaz, Kimberly D. Johnson, Peter Morris, James R. Rowbottom, John Daryl Thornton, Sheryl Feeney, and Alan Levine. "Dose of Early Therapeutic Mobility: Does Frequency or Intensity Matter?" Biological Research For Nursing 20, no. 5 (June 14, 2018): 522–30. http://dx.doi.org/10.1177/1099800418780492.

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Objective: Investigate the feasibility of a nurse-led mobility protocol and compare the effects of once- versus twice-daily episodes of early therapeutic mobility (ETM) and low- versus moderate-intensity ETM on serum biomarkers of inflammation and selected outcomes in critically ill adults. Design: Randomized interventional study with repeated measures and blinded assessment of outcomes. Setting: Four adult intensive care units (ICUs) in two academic medical centers. Subjects: Fifty-four patients with > 48 hr of mechanical ventilation (MV). Intervention: Patients were assigned to once- or twice-daily ETM via sealed envelope randomization at enrollment. Intensity of (in-bed vs. out-of-bed) ETM was administered according to protocolized patient assessment. Measurements: Interleukins 6, 10, 8, 15, and tumor necrosis factor-α were collected from serum before and after ETM; change scores were used in the analyses. Manual muscle and handgrip strength, delirium onset, duration of MV, and ICU length of stay (LOS) were evaluated as patient outcomes. Main Results: Hypotheses regarding the inflammatory biomarkers were not supported based on confidence intervals. Twice-daily intervention was associated with reduced ICU LOS. Moderate-intensity (out-of-bed) ETM was associated with greater manual muscle test scores and handgrip strength and reduced occurrence of delirium. Conclusion: Findings from this study suggest that nurses can provide twice-daily mobility interventions that include sitting on the edge of the bed once patients have a stable status without altering a pro-inflammatory serum biomarker profile.

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17

Band, Pierre R., Michele Deschamps, and Lucien Israël. "Retinoid Chemoprevention Timing and Dose Intensity." Cancer Investigation 7, no. 2 (January 1989): 205–10. http://dx.doi.org/10.3109/07357908909038286.

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18

Cohen, M. H. "What determines actual chemotherapy dose intensity?" Journal of Clinical Oncology 8, no. 11 (November 1990): 1926. http://dx.doi.org/10.1200/jco.1990.8.11.1926.

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19

Hryniuk, W. M., and M. Goodyear. "The calculation of received dose intensity." Journal of Clinical Oncology 8, no. 12 (December 1990): 1935–37. http://dx.doi.org/10.1200/jco.1990.8.12.1935.

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20

Heller, G., and N. K. Cheung. "Dose-intensity analysis and randomized trials." Journal of Clinical Oncology 9, no. 9 (September 1991): 1715–16. http://dx.doi.org/10.1200/jco.1991.9.9.1715.

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21

Ozols, Robert F. "Ovarian Cancer: Is Dose Intensity Dead?" Journal of Clinical Oncology 25, no. 27 (September 20, 2007): 4157–58. http://dx.doi.org/10.1200/jco.2007.12.1723.

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22

Cox, J., D. Ball, C. Belani, N. Choi, R. Gralla, J. Halle, R. Komaki, et al. "Dose intensity in lung cancer treatment." Lung Cancer 10 (March 1994): S11—S13. http://dx.doi.org/10.1016/0169-5002(94)91661-6.

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23

Sanchis-Gomar, Fabian, Carmen Fiuza-Luces, and Alejandro Lucia. "Exercise Intensity, Dose, and Cardiovascular Disease." JAMA 315, no. 15 (April 19, 2016): 1658. http://dx.doi.org/10.1001/jama.2016.0306.

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24

Gregory, S. A., and L. Trümper. "Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes?" Annals of Oncology 16, no. 9 (September 2005): 1413–24. http://dx.doi.org/10.1093/annonc/mdi264.

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25

Simon, R., and E. L. Korn. "Selecting Drug Combinations Based on Total Equivalent Dose (Dose Intensity)." JNCI Journal of the National Cancer Institute 82, no. 18 (September 19, 1990): 1469–76. http://dx.doi.org/10.1093/jnci/82.18.1469.

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26

Zelinskiy, A. S., G. A. Yakovlev, and D. E. Fil’trov. "Связь мощности дозы гамма-излучения с интенсивностью ливневых осадков." Вестник КРАУНЦ. Физико-математические науки, no. 3 (November 22, 2021): 189–99. http://dx.doi.org/10.26117/2079-6641-2021-36-3-189-199.

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Experimental and theoretical studies of the influence of the intensity, amount and duration of liquid atmospheric precipitation on the formation of γ-background in the surface layer of the atmosphere are presented. It was observed that precipitation causes an increase in the γ-radiation dose rate in the form of bursts. In this case, the total amount of precipitation in an event determines the magnitude of the burst of the dose rate, and the intensity of precipitation determines the rate of increase in the dose rate of γ-radiation. A mathematical model, which establishes a quantitative relationship between the dose rate of γ-radiation and the intensity (amount) of liquid atmospheric precipitation has been developed and verified (R2 = 0.93). Представлены экспериментальные и теоретические исследования влияния интенсивности, количества и продолжительности жидких атмосферных осадков на формирование γ-фона в приземном слое атмосферы. Было замечено, что осадки вызывают увеличение мощности дозы γ-излучения в виде всплесков. В этом случае общее количество осадков в событии определяет величину всплеска мощности дозы, а интенсивность осадков определяет скорость увеличения мощности дозы γ-излучения. Разработана и проверена математическая модель, устанавливающая количественную связь между мощностью дозы γ-излучения и интенсивностью (количеством) жидких атмосферных осадков (R2 = 0,93).

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27

Levin, L., and W. M. Hryniuk. "Dose intensity analysis of chemotherapy regimens in ovarian carcinoma." Journal of Clinical Oncology 5, no. 5 (May 1987): 756–67. http://dx.doi.org/10.1200/jco.1987.5.5.756.

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The relationship between outcome and dose intensity was analyzed for first-line chemotherapy of advanced ovarian cancer using a particular CHAP (cyclophosphamide, hexamethylmelamine, Adriamycin [Adria Laboratories, Columbus, OH], cisplatin) regimen as the standard. Previously described techniques were used to calculate the average dose intensity of regimens containing one, two, three, or all four drugs of CHAP, relative to the standard. The average relative dose intensity, especially the relative dose intensity of cisplatin, correlated significantly with clinical response and with median survival time (MST) of the entire group (not just the remitters). There was a distinct advantage for multiagent regimens over single alkylating agents and especially for multiagent regimens containing cisplatin. Survival correlated with response rate (of multiagent regimens). This analysis suggests that dose intensity is a determinant of treatment outcome. Prospective randomized trials would be required to test whether, and to what extent, dose intensity determines outcome independently of total amount of drug given, performance status, or other factors. If dose intensity does determine outcome, methods of increasing it should be tested in an attempt to improve treatment results.

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28

Hryniuk, W., E. Frei, and F. A. Wright. "A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: summation dose-intensity." Journal of Clinical Oncology 16, no. 9 (September 1998): 3137–47. http://dx.doi.org/10.1200/jco.1998.16.9.3137.

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PURPOSE To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer. MATERIALS AND METHODS First-line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes. RESULTS In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative. CONCLUSION A single-agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range.

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29

Campbell, Patrick G., Ian B. Stewart, Anita C. Sirotic, and Geoffrey M. Minett. "Does exercise intensity affect wellness scores in a dose-like fashion?" European Journal of Sport Science 20, no. 10 (January 7, 2020): 1395–404. http://dx.doi.org/10.1080/17461391.2019.1710264.

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30

Leavey, Patrick J., Elpis Mantadakis, and Gerhard Maale. "VARIABILITY IN DOSE INTENSITY OF HIGH-DOSE METHOTREXATE FOR NONMETASTATIC OSTEOSARCOMA." Pediatric Hematology and Oncology 19, no. 7 (January 2002): 483–89. http://dx.doi.org/10.1080/08880010290097305.

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31

Dembo, A. J. "Time-dose factors in chemotherapy: expanding the concept of dose-intensity." Journal of Clinical Oncology 5, no. 5 (May 1987): 694–96. http://dx.doi.org/10.1200/jco.1987.5.5.694.

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32

Smith, Malcolm, Jeffrey Abrams, Edward L. Trimble, and Richard S. Ungerleider. "Dose Intensity of Chemotherapy for Childhood Cancers." Oncologist 1, no. 5 (October 1996): 293–304. http://dx.doi.org/10.1634/theoncologist.1-5-293.

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33

de Vries, E. G. E., T. C. Hamilton, M. Lind, J. Dauplat, J. P. Neijt, and R. F. Ozols. "Drug resistance, supportive care and dose intensity." Annals of Oncology 4 (1993): S57—S62. http://dx.doi.org/10.1093/annonc/4.suppl_4.s57.

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34

Thigpen, J. T. "Dose-intensity in ovarian carcinoma: hold, enough?" Journal of Clinical Oncology 15, no. 4 (April 1997): 1291–93. http://dx.doi.org/10.1200/jco.1997.15.4.1291.

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35

Cohen, M. H. "MOPP dose intensity and survival: flawed analysis." Journal of Clinical Oncology 8, no. 4 (April 1990): 756–57. http://dx.doi.org/10.1200/jco.1990.8.4.756.

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36

Anderson, J. R., and P. F. Coccia. "Is more better? Dose intensity in neuroblastoma." Journal of Clinical Oncology 9, no. 6 (June 1991): 902–4. http://dx.doi.org/10.1200/jco.1991.9.6.902.

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37

Eijsvogels, Thijs M. H., and Paul D. Thompson. "Exercise Intensity, Dose, and Cardiovascular Disease—Reply." JAMA 315, no. 15 (April 19, 2016): 1659. http://dx.doi.org/10.1001/jama.2016.0312.

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38

Lutfi, Forat, Rohit Boshnoi, Vikas Patel, Aisha Alfasi, Michael Setteducato, Shuyao Zhang, Chintan Shah, et al. "Bleeding and Thrombotic Risk in Low Dose Heparin Infusion As Compared to Standard Dose Heparin Infusion." Blood 132, Supplement 1 (November 29, 2018): 1251. http://dx.doi.org/10.1182/blood-2018-99-110232.

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Abstract Introduction: At our institution, therapeutic use of unfractionated heparin (UFH) is administered by standard (target anti-Xa activity level 0.30 to 0.70 IU/mL) and low intensity (target anti-Xa activity level 0.25 to 0.35 IU/mL) protocols. In patients deemed high-risk for hemorrhage, the low intensity protocol is often employed. However, to date, there has been little study of differences in adverse events, namely hemorrhage, and efficacy between intensity protocols. Furthermore, identifying the effect of patient specific factors (e.g. age, indication for UFH, anticoagulant and antiplatelet use, medical, and surgical history) on outcomes has the potential to assist in determining the most optimal protocol. Methods: A total of 377 adult patients receiving therapeutic UFH from July 2011 to July 2017 at a single institution were retrospectively studied. Patients receiving UFH by acute coronary syndrome protocol and those receiving thrombolytics were excluded. IRB approval was obtained prior to collection of data. Results: Of the 377 patients, 42.0% (158/377) and 58.0% (219/377) were on low and standard intensity protocols, respectively. The majority of patients 76.1% (287/377) received an initial bolus. Patients were predominately Caucasian 74.0% (279/377), with median age of 63 years-old, and near equal gender distribution. The main indications for therapeutic UFH were venous thromboembolism VTE 46.9% (177/377) and atrial fibrillation 18.6% (70/377.) The indication for UFH was comparable between both groups with the exception of a higher percentage of those on full intensity protocol being treated for VTE (53.4% vs 38.0%.) Many patients were on home antiplatelet 35.0% (132/377) and anticoagulant 33.2% (125/377) therapy. The percentage of patients on aspirin, antiplatelet, and injectable anticoagulants was similar in both groups. A higher percentage of patients on low intensity protocol were on oral anticoagulants (36.1% vs 24.2%.) The median HAS-BLED score was two in both groups. Low intensity protocol patients were more likely to have had a history of previous bleeding (24.1% vs 12.8%) and had higher incidence of bleeding (10.8% vs 7.8%) than patients receiving standard intensity protocol. Transfusion requirement was greater in the low intensity protocol (29.7% vs 16.4%.) Both groups had similar risk of developing new thrombi (3.2% vs 3.7%) during the study period. All-cause mortality at three-months was higher in the low intensity group (19.6% vs 15.1%.) However, only 3.1% (2/64) of deaths within three-months were due to hemorrhage while on UFH and both were on the standard intensity protocol. Conclusion: Low intensity UFH infusion is used in patients in whom there is clinical concern for increased risk of bleeding. Bleeding rates with both low and standard intensity protocols was comparable (10.8% vs 7.8%), although patients on the low intensity protocol had notably higher transfusion rates (29.7% vs 16.4%.) Rates of new or worsening thrombi were comparable (3.2% vs 3.7%.) Initial analysis of our data suggests that there is not a clinically significant difference in studied outcomes between standard and low intensity protocols. Furthermore, in patients where this is high clinical risk of bleeding, a low intensity protocol can be utilized with similar therapeutic efficacy as a standard intensity protocol. Table Table. Disclosures No relevant conflicts of interest to declare.

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39

Jensen, Randy L., Merideth M. Wendland, Shyh-Shi Chern, and Dennis C. Shrieve. "NOVALIS INTENSITY-MODULATED RADIOSURGERY." Neurosurgery 62, suppl_5 (May 1, 2008): A2—A10. http://dx.doi.org/10.1227/01.neu.0000325931.26531.45.

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ABSTRACT OBJECTIVE The Novalis stereotactic radiotherapy system (BrainLAB, Heimstetten, Germany) allows for precise treatment of cranial base tumors with single-fraction radiosurgery. In some cases, however, proximity of the optic nerve and chiasm is a concern. In these cases, intensity-modulated stereotactic radiosurgery (IMRS) can be used to limit the dose to these structures. IMRS planning can be labor intensive, which poses a problem when it is performed on the day of treatment. We describe our methods and results of preprocedure planning for IMRS for patients with lesions in the cavernous sinus or parasellar regions in whom the dose to the optic nerve or chiasm might exceed our acceptable tolerance dose (8 Gy). METHODS Patients whose lesions were more than 4 mm from the optic nerve and chiasm on standard magnetic resonance imaging scans but who were questionable candidates for radiosurgery because of concerns of dose to the optic nerve or chiasm were considered for IMRS. Preprocedure imaging (computed tomography and magnetic resonance imaging) was fused and analyzed using the BrainLAB BrainScan 5.3 treatment planning system. Dynamic conformal arc plans for stereotactic radiosurgery and IMRS were evaluated. Doses to the planning target volume and optic apparatus were assessed by dose-volume histograms and conformality index calculated to characterize the quality of the different plans. When IMRS was used, the preplan allowed for a rapid recalculation on the treatment day, minimizing the time patients were in the head frame before treatment. RESULTS We describe three patients with recurrent pituitary tumors and three with meningiomas. Doses were 1500 to 2000 cGy prescribed to the 80 to 96% isodose line delivered by eight to 22 fields. Tumor volumes ranged from 2.70 to 8.82 cm3 (mean, 5.7 cm3). In five of the six patients, the dynamic conformal arc plan precluded delivery of therapeutic dose without exceeding optic nerve tolerance. On the basis of 95% coverage of target volume, maximum prescription doses of 7.7 to 20.64 Gy were possible with the dynamic conformal arc plans without exceeding 8 Gy to the optic apparatus. IMRS allowed maximum doses of 20 to 31 Gy using the same optic apparatus dose restriction. No complications have occurred, and all tumors have remained stable since treatment (mean follow-up period, 30 mo). CONCLUSION We believe this pretreatment technique streamlines the process for IMRS, allowing for better patient comfort and efficient physician time use.

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40

Komuro, Ayumi, Sachiko Seo, Nobuo Mochizuki, Yosuke Minami, and Toshikatu Kawasaki. "Impact of Total Dose Intensity and Relative Dose Intensity (RDI) of R-CHOP on Survival in Patients with DLBCL." Blood 132, Supplement 1 (November 29, 2018): 4218. http://dx.doi.org/10.1182/blood-2018-99-114227.

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Abstract Background: The standard chemotherapy for diffuse large B-cell lymphoma (DLBCL) is CHOP combined with rituximab (R-CHOP). The guidelines (e.g. NCCN or ESMO) recommend six to eight courses of R-CHOP and the optimal number of courses is still unclear. The relative dose intensity (RDI) was proposed as an indicator for both dose intensity and interval. The previous studies have reported the relation between RDI of CHOP or R-CHOP and treatment outcomes. However, little is known about the low threshold of RDI that affects survival and few studies have compared between RDI and total dose of R-CHOP in the effect on survival. In this study, we evaluated the effect of total dose and RDI of R-CHOP on survival in patients with DLBCL. Patients and methods: We retrospectively analyzed 190 patients with newly diagnosed DLBCL who completed more than 6 courses of R-CHOP between January 2013 and December 2016 at our center. Dose reduction of the CHOP regimen was considered in patients over 70 years of age. RDI was calculated as the ratio of delivered dose intensity (mg/m2/week) to the planned dose intensity (mg/m2/week) and was shown as a percentage. The average of RDI in each drug of R-CHOP was used for the analyses. Risk factors for overall mortality were analyzed using Cox proportional hazards models. Results: Among the 190 patients, median age was 70.0 years (range, 34-91). The numbers of patients were 15, 55, 46, and 66 in low, low-intermediate, high-intermediate, and high risk groups based on the International Prognostic Index (IPI), respectively. Three-year overall survival (OS) was 88%, 100%, and 83% in the patients with 6 (N=64), 7 (N=3), and 8 (N=123) courses of R-CHOP, respectively (p = 0.55). Median RDI was 92% (range, 32 to 117) and the lower quartile of RDI was 72%. Probabilities of OS by the quartile of RDI were shown in Figure 1 and OS was significantly worse in the patients with <72% of RDI than those with ≥72% of RDI (3-year OS, 66% vs 90%; p = 0.001). Subgroup analysis by age (<70 or ≥70 years) showed the similar trend toward worse survival in patients with <72% of RDI in both age groups (<70 years, p=0.001; ≥70 years, p = 0.054). In multivariable analysis, RDI less than 72% (HR, 2.94; 95% CI, 1.25-6.90, p = 0.014) was a significantly important risk factor for mortality, while IPI (HR, 3.2; 95% CI, 0.9-11.4, p = 0.07) or the number of courses of R-CHOP (HR, 1.66; 95% CI, 0.59-4.64, p = 0.34) was not. When analyzing RDI as a continuous variable, RDI (HR, 1.03; 95% CI, 1.01-1.05, p = 0.009) and IPI (HR, 1.49; 95% CI, 1.05-2.12, p = 0.027) were identified as significant risk factors for mortality. Similarly, patients with <72% of RDI had significantly worse progression-free survival (PFS) than those with ≥72% of RDI (Figure 2, 3-year PFS, 59% vs 80%; p = 0.001). However, RDI was not a significantly important risk factor for PFS after adjusting for several factors. Among 190 patients in our cohort, 24 patients died and 17 patients died from recurrence of DLBCL. There is no difference in the number of recurrence between the patients with <72% (N=6) and ≥72% (N=11) of RDI (p = 0.18). Conclusions: Higher RDI of R-CHOP was significantly associated with a higher survival rate in patients with DLBCL, although it did not reach statistical significance in patients over 70 years of age. More than 72% of RDI should be maintained to obtain better OS and PFS. Increase of total dose of R-CHOP was not related to better survival, resulting from the analysis using the number of treatment courses. We conclude that 6 courses of R-CHOP therapy with higher RDI would be recommended for all ages. Further studies are needed to validate our findings. Disclosures Minami: Novartis Pharma K.K.: Consultancy; Takeda Pharmaceutical Company Limited.: Consultancy; ONO PHARMACEUTICAL CO., LTD: Research Funding.

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LeVasseur, N., and S. K. Chia. "Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?" British Journal of Cancer 117, no. 2 (June 22, 2017): 157–58. http://dx.doi.org/10.1038/bjc.2017.176.

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Alghamdi, Mohammed Abdullah, Richard Lee-Ying, Mina Swiha, Kelvin K. Chan, Winson Y. Cheung, Maria Ho, and Vincent C. Tam. "The effect of sorafenib (S) starting dose and dose intensity on survival in patients with advanced hepatocellular carcinoma (HCC)." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 400. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.400.

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400 Background: The SHARP trial showed that S improves survival in advanced HCC. In clinical practice full dose (FD) of S at 400mg bid can be difficult to tolerate and so a reduced dose (RD) is often required. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival in patients with HCC. Methods: All patients treated with S for HCC in Alberta, Canada from January 2008 to July 2016 were included in this study. Patient demographics, clinical, tumor characteristics, S starting dose and dose intensity were collected and analyzed. Patients were dichotomized into starting FD or RD of S. A mean dose intensity of > 75% and < / = 75% were considered normal and reduced, respectively. Survival outcomes were assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity and relevant clinical and pathologic factors to assess their impact on survival. Results: A total of 156 patients were included. Median age was 63, 78% were men, 34% were East Asian, 77% were Childs-Pugh A, and the most common causes of liver disease were hepatitis B (30%) and C (30%). Most patients had EGOG performance status of 0 and 1 prior to starting S (29% and 62%, respectively). S was started at FD in 58% of patients and 50% had a dose intensity > 75%. The median survival for both starting FD and RD was 10.3 months, and not significantly different (p = 0.14).The median survival for a dose intensity > 75% vs < / = 75% was 10.7 vs 9.5 months, respectively (p = 0.76). In multivariable models that adjusted for demographic, stage, performance status and liver function, starting dose (HR 0.8 95%CI 0.5-1.2) and dose intensity (HR0.9 95% CI 0.6-1.4) were not associated with survival. Conclusions: Starting S with a RD may be a reasonable strategy for HCC, since it does not appear to impact survival. Also, dose intensity did not impact survival, suggesting that additional dose modifications may not compromise effectiveness. Though limited by small numbers, we are planning to confirm these findings in a larger, pan-Canadian dataset.

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Meyer, R. M., W. M. Hryniuk, and M. D. Goodyear. "The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin's lymphoma." Journal of Clinical Oncology 9, no. 2 (February 1991): 339–47. http://dx.doi.org/10.1200/jco.1991.9.2.339.

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To determine whether the dose intensity of chemotherapeutic regimens correlates with the complete remission rate in adult patients with advanced-stage intermediate-grade lymphoma, reports of comparative trials of therapy were reviewed. Reports were identified using MEDLINE, through references from review articles, and through review of selected abstracts. Twenty-two studies including 14 randomized and eight cohort trials were analyzed to assess projected dose intensity. Four other studies were analyzed to assess the role of received dose intensity. Dose intensities were calculated using described methods and correlated with complete remission rates. Individual trials were assessed using "levels of evidence." A metaanalysis of randomized trials and a cross-trial analysis of all comparative trials using a weighted least squares linear regression were performed. Using levels of evidence, support was obtained for the hypothesis that dose intensity correlates with the remission rate from two trials in which dose intensity was "indirectly" tested. As these studies did not "directly" test dose intensity, confounding variables, including those arising from the assumptions made in calculating dose intensity, cannot be excluded. Metaanalysis showed a relative probability of achieving complete remission of 1.34 (95% confidence interval, 1.13 to 1.58) favoring the pooled arm of high dose intensity. Cross-trial analysis showed a relatively weak association between dose intensity and remission rate (r = .49, P = .0001). Two of four reports retrospectively assessing received dose intensity suggested that increased dose intensity is associated with superior remission rates. These analyses suggest that dose intensity may correlate with the remission rate in advanced-stage intermediate-grade lymphoma. However, properly designed trials directly testing dose intensity have not been performed and are needed to confirm this hypothesis.

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NISHIMURA, MEIKO, TAKUMA ONOE, HIDEKI SAKAI, MINORI ARASE, SAYURI WATANABE, MISAO SOYAMA, KAZUKI HASHIMOTO, et al. "Safety and Relative Dose Intensity of Dose-dense Doxorubicin and Cyclophosphamide Followed by Dose-dense Paclitaxel." Anticancer Research 39, no. 8 (July 31, 2019): 4379–83. http://dx.doi.org/10.21873/anticanres.13607.

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Norton, Larry. "Dose-Intensity, Dose-Escalation, and Dose-Density in the Adjuvant Chemotherapy of Primary, Operable Breast Cancer." Breast Disease 14, no. 1 (December 1, 2001): 81–89. http://dx.doi.org/10.3233/bd-2001-14109.

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Fuss, Martin, and Bill J. Salter. "Intensity-Modulated Radiosurgery: Improving Dose Gradients and Maximum Dose Using Post Inverse-Optimization Interactive Dose Shaping." Technology in Cancer Research & Treatment 6, no. 3 (June 2007): 197–203. http://dx.doi.org/10.1177/153303460700600307.

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Sandler, Howard M. "Exploring Dose-Intensity: Carefully Comparing High-Dose With Low-Dose External-Beam Radiotherapy for Prostate Cancer." Journal of Clinical Oncology 24, no. 13 (May 1, 2006): 1975–77. http://dx.doi.org/10.1200/jco.2006.05.7612.

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Cherney, Leora R. "Aphasia treatment: Intensity, dose parameters, and script training." International Journal of Speech-Language Pathology 14, no. 5 (June 26, 2012): 424–31. http://dx.doi.org/10.3109/17549507.2012.686629.

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Pollera, C. F., A. Pietrangeli, and D. Giannarelli. "Cisplatin-induced peripheral neurotoxicity: Relationship to dose intensity." Annals of Oncology 2, no. 3 (March 1991): 212. http://dx.doi.org/10.1093/oxfordjournals.annonc.a057907.

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Neijt, Jan P. "The challenge of dose-intensity in ovarian cancer." Annals of Oncology 4, no. 5 (May 1993): 349–50. http://dx.doi.org/10.1093/oxfordjournals.annonc.a058512.

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