Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Surgery
2.2. Radiotherapy
2.3. Chemotherapy
2.4. Psycho-Oncologic Advice
2.5. Endpoint and Statistics
3. Results
3.1. Radiotherapy
3.2. Chemotherapy
4. Discussion
5. Limitations of This Study
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Strauss, S.J.; Frezza, A.M.; Abecassis, N.; Bajpai, J.; Bauer, S.; Biagini, R.; Bielack, S.; Blay, J.Y.; Bolle, S.; Bonvalot, S.; et al. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 2021, 32, 1520–1536. [Google Scholar] [CrossRef]
- Gronchi, A.; Miah, A.B.; Dei Tos, A.P.; Abecassis, N.; Bajpai, J.; Bauer, S.; Biagini, R.; Bielack, S.; Blay, J.Y.; Bolle, S.; et al. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up(☆). Ann. Oncol. 2021, 32, 1348–1365. [Google Scholar] [CrossRef]
- Rose, P.S. What’s New in Musculoskeletal Tumor Surgery. J. Bone Joint Surg. Am. 2021, 103, 2251–2260. [Google Scholar] [CrossRef] [PubMed]
- O’Sullivan, B.; Davis, A.M.; Turcotte, R.; Bell, R.; Catton, C.; Chabot, P.; Wunder, J.; Kandel, R.; Goddard, K.; Sadura, A.; et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial. Lancet 2002, 359, 2235–2241. [Google Scholar] [CrossRef] [PubMed]
- Payne, W.G.; Naidu, D.K.; Wheeler, C.K.; Barkoe, D.; Mentis, M.; Salas, R.E.; Smith, D.J., Jr.; Robson, M.C. Wound healing in patients with cancer. Eplasty 2008, 8, e9. [Google Scholar] [PubMed]
- Issels, R.D.; Lindner, L.H.; Verweij, J.; Wessalowski, R.; Reichardt, P.; Wust, P.; Ghadjar, P.; Hohenberger, P.; Angele, M.; Salat, C.; et al. Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients with Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial. JAMA Oncol. 2018, 4, 483–492. [Google Scholar] [CrossRef]
- Lebas, A.; Le Fevre, C.; Waissi, W.; Chambrelant, I.; Brinkert, D.; Noel, G. Prognostic Factors in Extremity Soft Tissue Sarcomas Treated with Radiotherapy: Systematic Review of the Literature. Cancers 2023, 15, 4486. [Google Scholar] [CrossRef]
- Aizer, A.A.; Chen, M.H.; Parekh, A.; Choueiri, T.K.; Hoffman, K.E.; Kim, S.P.; Martin, N.E.; Hu, J.C.; Trinh, Q.D.; Nguyen, P.L. Refusal of curative radiation therapy and surgery among patients with cancer. Int. J. Radiat. Oncol. Biol. Phys. 2014, 89, 756–764. [Google Scholar] [CrossRef]
- Bilgeri, A.; Klein, A.; Lindner, L.H.; Nachbichler, S.; Knosel, T.; Birkenmaier, C.; Jansson, V.; Baur-Melnyk, A.; Durr, H.R. The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough? Cancers 2020, 12, 2560. [Google Scholar] [CrossRef]
- Trojani, M.; Contesso, G.; Coindre, J.M.; Rouesse, J.; Bui, N.B.; de Mascarel, A.; Goussot, J.F.; David, M.; Bonichon, F.; Lagarde, C. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int. J. Cancer 1984, 33, 37–42. [Google Scholar] [CrossRef]
- Issels, R.D.; Lindner, L.H.; Verweij, J.; Wust, P.; Reichardt, P.; Schem, B.C.; Abdel-Rahman, S.; Daugaard, S.; Salat, C.; Wendtner, C.M.; et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: A randomised phase 3 multicentre study. Lancet Oncol. 2010, 11, 561–570. [Google Scholar] [CrossRef] [PubMed]
- Smeland, S.; Bielack, S.S.; Whelan, J.; Bernstein, M.; Hogendoorn, P.; Krailo, M.D.; Gorlick, R.; Janeway, K.A.; Ingleby, F.C.; Anninga, J.; et al. Survival and prognosis with osteosarcoma: Outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur. J. Cancer 2019, 109, 36–50. [Google Scholar] [CrossRef] [PubMed]
- Ferrari, S.; Bielack, S.S.; Smeland, S.; Longhi, A.; Egerer, G.; Sundby Hall, K.; Donati, D.; Kevric, M.; Brosjo, O.; Comandone, A.; et al. EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma. Tumori 2018, 104, 30–36. [Google Scholar] [CrossRef] [PubMed]
- Anderton, J.; Moroz, V.; Marec-Berard, P.; Gaspar, N.; Laurence, V.; Martin-Broto, J.; Sastre, A.; Gelderblom, H.; Owens, C.; Kaiser, S.; et al. International randomised controlled trial for the treatment of newly diagnosed EWING sarcoma family of tumours—EURO EWING 2012 Protocol. Trials 2020, 21, 96. [Google Scholar] [CrossRef] [PubMed]
- Dias, L.M.; Bezerra, M.R.; Barra, W.F.; Rego, F. Refusal of medical treatment by older adults with cancer: A systematic review. Ann. Palliat. Med. 2021, 10, 4868–4877. [Google Scholar] [CrossRef] [PubMed]
- Gopal, N.; Kozikowski, A.; Barginear, M.F.; Fishbein, J.; Pekmezaris, R.; Wolf-Klein, G. Reasons for Chemotherapy Refusal or Acceptance in Older Adults with Cancer. South Med. J. 2017, 110, 47–53. [Google Scholar] [CrossRef] [PubMed]
- Puts, M.T.; Tapscott, B.; Fitch, M.; Howell, D.; Monette, J.; Wan-Chow-Wah, D.; Krzyzanowska, M.; Leighl, N.B.; Springall, E.; Alibhai, S.M. A systematic review of factors influencing older adults’ decision to accept or decline cancer treatment. Cancer Treat. Rev. 2015, 41, 197–215. [Google Scholar] [CrossRef] [PubMed]
- Levin, M.; Mermelstein, H.; Rigberg, C. Factors associated with acceptance or rejection of recommendation for chemotherapy in a community cancer center. Cancer Nurs. 1999, 22, 246–250. [Google Scholar] [CrossRef]
- Reddy, V.K.; Jain, V.; Venigalla, S.; Levin, W.P.; Wilson, R.J.; Weber, K.L.; Kalbasi, A.; Sebro, R.A.; Shabason, J.E. Radiotherapy Remains Underused in the Treatment of Soft-Tissue Sarcomas: Disparities in Practice Patterns in the United States. J. Natl. Compr. Cancer Netw. 2021, 19, 295–306. [Google Scholar] [CrossRef]
- Coaston, T.N.; Sakowitz, S.; Chervu, N.L.; Branche, C.; Shuch, B.M.; Benharash, P.; Revels, S. Persistent racial disparities in refusal of resection in non-small cell lung cancer patients at high-volume and Black-serving institutions. Surgery 2023, 174, 1428–1435. [Google Scholar] [CrossRef]
- Iacobucci, G. Older people are no more likely to refuse cancer treatment than younger patients, survey finds. BMJ 2015, 351, h4526. [Google Scholar] [CrossRef] [PubMed]
- Konigsberg, R.D. Refuseniks. Why some cancer patients reject their doctor’s advice. Time 2011, 177, 72–74, 77. [Google Scholar]
- Jorgensen, M.L.; Young, J.M.; Solomon, M.J. Adjuvant chemotherapy for colorectal cancer: Age differences in factors influencing patients’ treatment decisions. Patient Prefer. Adherence 2013, 7, 827–834. [Google Scholar] [CrossRef] [PubMed]
- Venigalla, S.; Carmona, R.; VanderWalde, N.; Sebro, R.; Sharma, S.; Simone, C.B., 2nd; Wilson, R.J., 2nd; Weber, K.L.; Shabason, J.E. Disparities in Perioperative Radiation Therapy Use in Elderly Patients with Soft-Tissue Sarcoma. Int. J. Radiat. Oncol. Biol. Phys. 2018, 102, 155–165. [Google Scholar] [CrossRef] [PubMed]
- Colson-Fearon, D.; Stone, R.; Viswanathan, A.N. Risk Factors and Survival Impact Associated with Documentation of Radiation Therapy Refusal in Patients with Gynecologic Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2023, in press. [CrossRef]
- Liu, J.; Zhu, Z.; Hua, Z.; Lin, W.; Weng, Y.; Lin, J.; Mao, H.; Lin, L.; Chen, X.; Guo, J. Radiotherapy refusal in breast cancer with breast-conserving surgery. Radiat. Oncol. 2023, 18, 130. [Google Scholar] [CrossRef]
- Kachare, S.D.; Brinkley, J.; Vohra, N.A.; Zervos, E.E.; Wong, J.H.; Fitzgerald, T.L. Radiotherapy associated with improved survival for high-grade sarcoma of the extremity. J. Surg. Oncol. 2015, 112, 338–343. [Google Scholar] [CrossRef]
- Nassin, M.L.; Mueller, E.L.; Ginder, C.; Kent, P.M. Family Refusal of Chemotherapy for Pediatric Cancer Patients: A National Survey of Oncologists. J. Pediatr. Hematol. Oncol. 2015, 37, 351–355. [Google Scholar] [CrossRef]
- Caruso Brown, A.E.; Slutzky, A.R. Refusal of Treatment of Childhood Cancer: A Systematic Review. Pediatrics 2017, 140, e20171951. [Google Scholar] [CrossRef]
- Benedetti, D.J.; Beskow, L.M.; Brown, A.E.C. Overcoming refusal of treatment in pediatric cancer without legal involvement: A descriptive case series from interviews with pediatric oncologists. Pediatr. Blood Cancer 2023, 70, e30656. [Google Scholar] [CrossRef]
- Ayanian, J.Z.; Zaslavsky, A.M.; Fuchs, C.S.; Guadagnoli, E.; Creech, C.M.; Cress, R.D.; O’Connor, L.C.; West, D.W.; Allen, M.E.; Wolf, R.E.; et al. Use of adjuvant chemotherapy and radiation therapy for colorectal cancer in a population-based cohort. J. Clin. Oncol. 2003, 21, 1293–1300. [Google Scholar] [CrossRef]
- Hamidi, M.; Moody, J.S.; Kozak, K.R. Refusal of radiation therapy and its associated impact on survival. Am. J. Clin. Oncol. 2010, 33, 629–632. [Google Scholar] [CrossRef]
- Schwam, Z.G.; Husain, Z.; Judson, B.L. Refusal of postoperative radiotherapy and its association with survival in head and neck cancer. Radiother. Oncol. 2015, 117, 343–350. [Google Scholar] [CrossRef] [PubMed]
- Moya, J.J.; Moazzez, A.; Ozao-Choy, J.J.; Dauphine, C. Patients with Invasive Breast Cancer Who Refuse Treatment: An Analysis of Associated Factors and Impact on Survival. Am. Surg. 2021, 87, 1627–1632. [Google Scholar] [CrossRef] [PubMed]
- Salti, I.; Petesch, T.; Naffouje, S.A.; Kamarajah, S.K.; Dahdaleh, F. Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database. Am. Surg. 2023, 89, 4644–4653. [Google Scholar] [CrossRef] [PubMed]
- Amini, A.; Verma, V.; Li, R.; Vora, N.; Kang, R.; Gernon, T.J.; Chang, S.; Karam, S.; Massarelli, E.; Maghami, E.G.; et al. Factors predicting for patient refusal of head and neck cancer therapy. Head Neck 2020, 42, 33–42. [Google Scholar] [CrossRef] [PubMed]
- Johnson, S.B.; Park, H.S.; Gross, C.P.; Yu, J.B. Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients with Curable Cancers. JAMA Oncol. 2018, 4, 1375–1381. [Google Scholar] [CrossRef]
- Guadagnolo, B.A.; Bassett, R.L.; Mitra, D.; Farooqi, A.; Hempel, C.; Dorber, C.; Willis, T.; Wang, W.L.; Ratan, R.; Somaiah, N.; et al. Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): A single-centre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2022, 23, 1547–1557. [Google Scholar] [CrossRef]
- Spalek, M.J.; Borkowska, A.M.; Telejko, M.; Wagrodzki, M.; Niebylowska, D.; Uzar, A.; Bialobrzeska, M.; Rutkowski, P. The Feasibility Study of Hypofractionated Radiotherapy with Regional Hyperthermia in Soft Tissue Sarcomas. Cancers 2021, 13, 1332. [Google Scholar] [CrossRef]
- Gilbar, O. The attitude of the doctor to the refusal of the cancer patient to accept chemotherapy. Med. Law 1989, 8, 527–534. [Google Scholar]
- Landrum, M.B.; Keating, N.L.; Lamont, E.B.; Bozeman, S.R.; McNeil, B.J. Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration. Cancer 2012, 118, 3345–3355. [Google Scholar] [CrossRef] [PubMed]
- Huijer, M.; van Leeuwen, E. Personal values and cancer treatment refusal. J. Med. Ethics 2000, 26, 358–362. [Google Scholar] [CrossRef] [PubMed]
- Bickell, N.A.; Weidmann, J.; Fei, K.; Lin, J.J.; Leventhal, H. Underuse of breast cancer adjuvant treatment: Patient knowledge, beliefs, and medical mistrust. J. Clin. Oncol. 2009, 27, 5160–5167. [Google Scholar] [CrossRef] [PubMed]
- Frenkel, M. Refusing treatment. Oncologist 2013, 18, 634–636. [Google Scholar] [CrossRef]
Entities | N | % |
---|---|---|
Undifferentiated pleomorphic sarcoma (UPS) | 164 | 20% |
Liposarcoma | 152 | 18% |
Chondrosarcoma | 113 | 14% |
Osteosarcoma | 86 | 10% |
Myxofibrosarcoma | 68 | 8% |
Leiomyosarcoma | 54 | 7% |
Synovial sarcoma | 36 | 4% |
Ewing sarcoma | 26 | 3% |
Malignant peripheral nerve sheath tumor (MPNST) | 23 | 3% |
Fibrosarcoma | 21 | 3% |
Other lesions | 85 | 10% |
Tumor Characteristics | N | % |
---|---|---|
Soft tissue | 609 | 74% |
Bone | 219 | 26% |
Primary disease | 691 | 83% |
Recurrent disease | 137 | 17% |
Deep | 735 | 89% |
Superficial | 93 | 11% |
Size > 5 cm | 491 | 59% |
Size ≤ 5 cm | 337 | 41% |
G1 * | 187 | 23% |
G2 * | 249 | 30% |
G3 * | 345 | 42% |
GX + | 47 | 6% |
No metastatic disease | 756 | 91% |
Metastatic disease | 72 | 9% |
Factor | p | HR | 95% CI |
---|---|---|---|
Grading | <0.0001 | 2.16 | 1.70–2.73 |
Primary/Recurrent tumor | 0.0513 | 1.43 | 1.00–2.05 |
Deep location | 0.3814 | 1.30 | 0.72–2.34 |
Size > 5 cm | 0.0001 | 2.11 | 1.47–3.04 |
Age | <0.0001 | 1.03 | 1.02–1.04 |
Metastatic disease at surgery | <0.0001 | 4.05 | 2.72–6.01 |
Refusal of RTx | <0.0001 | 3.05 | 1.93–4.82 |
Refusal of CTx | 0.1515 | 0.64 | 0.34–1.18 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mentrup, F.; Klein, A.; Lindner, L.H.; Nachbichler, S.; Holzapfel, B.M.; Albertsmeier, M.; Knösel, T.; Dürr, H.R. Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk. Cancers 2024, 16, 239. https://doi.org/10.3390/cancers16020239
Mentrup F, Klein A, Lindner LH, Nachbichler S, Holzapfel BM, Albertsmeier M, Knösel T, Dürr HR. Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk. Cancers. 2024; 16(2):239. https://doi.org/10.3390/cancers16020239
Chicago/Turabian StyleMentrup, Franziska, Alexander Klein, Lars Hartwin Lindner, Silke Nachbichler, Boris Michael Holzapfel, Markus Albertsmeier, Thomas Knösel, and Hans Roland Dürr. 2024. "Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk" Cancers 16, no. 2: 239. https://doi.org/10.3390/cancers16020239
APA StyleMentrup, F., Klein, A., Lindner, L. H., Nachbichler, S., Holzapfel, B. M., Albertsmeier, M., Knösel, T., & Dürr, H. R. (2024). Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk. Cancers, 16(2), 239. https://doi.org/10.3390/cancers16020239