|Year : 2021 | Volume
| Issue : 4 | Page : 222-228
Cancer-related fibrosis: Prevention or treatment? – A descriptive review
Renu Pattanshetty, Mounica Srinivas Rao
Department of Oncology Physiotherapy, KAHER Institute of Physiotherapy, Belagavi, Karnataka, India
|Date of Submission||19-Jul-2021|
|Date of Decision||25-Jul-2021|
|Date of Acceptance||30-Jul-2021|
|Date of Web Publication||22-Mar-2022|
Dr. Renu Pattanshetty
Department of Oncology Physiotherapy, KAHER Institute of Physiotherapy, Belagavi
Source of Support: None, Conflict of Interest: None
Cancer and its therapies, including surgeries, radiation therapy, and chemotherapy, have a significant influence on the body of the patient. Tissue fibrosis is one of the most significant adverse effects noticed in cancer patients. Fibrosis caused by any tissue damage or various intracellular mechanisms can result in physical and functional impairments such as trismus, neuro-musculoskeletal dysfunction syndromes, fibrosis, speech and swallowing dysfunctions, upper limb and lower limb impairments, and sexual dysfunctions, all of which have a negative impact on patients' quality of life. Using manual therapy and therapeutic modalities, speech and swallowing therapy, and vocational rehabilitation are some of the important approaches to treating postcancer treatment problems. As a result, when to begin rehabilitation to enhance and maintain functional and physical performance becomes critical.
Keywords: Cancer-related fibrosis, cancer, pathophysiology, physical therapy, quality of life, rehabilitation
|How to cite this article:|
Pattanshetty R, Rao MS. Cancer-related fibrosis: Prevention or treatment? – A descriptive review. J NTR Univ Health Sci 2021;10:222-8
| Introduction|| |
Cancer, as defined by the National Cancer Institute, is the uncontrollable proliferation of normal cells in the body with the potential to spread to other regions of the body. According to GLOBOCAN 2020 statistics, cancer is the largest cause of death and disability, as well as a barrier to life expectancy globally. Anticipated 19.3 million new cases and 10 million cancer deaths worldwide, with Asia accounting for 49.3% of cases and a mortality rate of 58.3%, is a great cause of concern since the deaths are due to secondary morbidities. Cancers of the breast (female), lung, prostate, nonmelanoma of the skin, and gastrointestinal (GI) cancer top the list in terms of new cases. According to the expected incidence of cancer data in India for 2020, a total of 1,392,179 cases have been documented, with GI cancer being the most common, followed by malignancies of the oral cavity and throat.
Tissue fibrosis in cancer patients can result in significant morbidity and death globally, which may be caused by the disease or its therapies. Tissue damage and fibrosis are caused by different medical procedures such as radiotherapy, chemotherapy, and surgery. Not only do tumor cells interact with the surrounding cells, stromal cells and extracellular matrix, immune cells, and soluble signaling molecules in order to survive and thrive, but they also interact and form a microenvironment for the tumor. With increased mechanical stress, fibrosis can raise the risk of malignancy, which commonly manifests as substantial extracellular matrix buildup. Fibrosis can manifest as inflammation, excessive extracellular matrix deposition, linearization, and cross-linking., The present review has attempted to describe the pathophysiology of cancer-related fibrosis due to cancer treatments and physical therapy.
| Pathophysiology|| |
Fibrosis is characterized by the accumulation of excess connective tissue, which results in stromal hardness and scar formation as well as poor epithelial healing. The extracellular matrix is remodeled via fibroblast deposition and matrix metalloproteinase secretion. Fibroblasts are the cells that are primarily responsible for fibrosis in both normal and pathologic environments. Fibrocytes, the progenitors of fibroblasts, and myeloid-derived suppressor cells, which promote tumor-associated fibrosis, are repressed in cancer. Other cells, such as mesenchymal stem cells, which aid in wound healing, and stellate cells, which influence immune responses to decrease inflammation and aid in tissue repair via differentiation, play a significant part in cancer-related fibrosis. Because cancer produces persistent inflammation and damage, it can result in fibrosis as part of the tissue remodeling and healing process. Instead of a typical, healthy reformed tissue, the tissue undergoes a continual fibrotic transformation. Cancer-associated fibrosis is said to be caused by this nonhealing pattern of damage.,,,,, [Figure 1]
Cancer treatment options including surgeries, radiation therapy (RT), chemotherapy, immunotherapy, and other innovative targeted medicines are also said to have a role in inducing cancer-related fibrosis leading to tissue damage as a reaction to repair by either one of two mechanisms: radiolytic hydrolysis or activation of the innate immune response.,
| Radiation Therapy And Its Role In Cancer-Related Fibrosis|| |
During radiotherapy, the treated area is subjected to ionizing radiation causing free radicals to be released, resulting in biological consequences such as DNA damage. The release of free radicals promotes the development of fibrotic diseases such as idiopathic pulmonary fibrosis, liver fibrosis, and kidney fibrosis by increasing oxidative stress, which is the imbalance between the production of reactive oxygen species and the cell's ability to elicit an effective antioxidant response., For example, individuals with head and neck cancer who undergo RT may experience side effects from the treatment harming the healthy tissue. This can result in secretion thickening, increased infection risk, discomfort and sensory abnormalities, tissue fibrosis, and salivary gland dysfunction. Oral mucositis is an acute reaction to RT that appears in the first 2–3 weeks and escalates to ulceration and pseudomembranes as the RT continues. This is connected to the radiation dosage distribution and nonkeratinized oral tissue causing dermatitis. Oropharyngeal candidiasis is notably prevalent in individuals with head and neck cancer, which may spread to the esophagus, causing mucosal discomfort, taste changes, and dysphagia. There may be no burning sensitivity or pain, and leading to a coating feeling in their mouth, odynophagia, dysgeusia, and the odor of yeast infection. Such alterations can result in fibrosis of the mucosal membrane in the oral cavity, known as oral submucosal fibrosis. As the disease and/or therapy develops, this might result in leukoplakia, scarring, and trismus. It is postulated that the transforming growth factor (TGF) signal transduction pathway, which attribute significantly to collagen synthesis and inhibits collagen degradation by inducing the activity of tissue inhibitor of matrix metalloproteinase gene, causes oversynthesis of collagen by increased levels of connective tissue growth factor. This is said to result in the development of fibrosis.,,, Posttreatment complications for patients with lung cancer, breast cancer, and lymphomas include radiation pneumonitis, pulmonary fibrosis, emphysema, respiratory difficulties, cardiac fibrosis, scar tissue development, and persistent arm lymphedema as a result of RT, chemotherapy, or surgery. Radiation to the thorax puts the lungs and heart at more danger. More than 50 Grays (Gy) of RT has the potential to cause lung tissue damage, resulting in pneumonitis or fibrosis. Typically, 10–20% of irradiated patients get moderate to severe radiation-induced pneumonitis, which is thought to be caused by alveolar destruction triggering an inflammatory reaction in the lungs' interstitial space. Because of the increased vascular permeability, this creates edema. Within 12 weeks of radiotherapy, 1–16% of patients get symptomatic with shortness of breath. Radiation with a higher dosage per fraction of 2.5–2.75 Gy may result in this type of symptomatic pneumonitis. Pneumonitis is said to cause pulmonary fibrosis later in life. When paired with chemotherapy, radiation may have a combined severe adverse effect. The lung anomaly appears 4–8 months after breast radiation treatment.,,
Significant morphological vaginal alterations with increasing dosage are seen to occur in cervical cancer survivors. Mucosal atrophy was seen in 91% of the survivors, as was pelvic fibrosis in 97%. High-density collagen was found in the connective tissue of individuals who had received external radiation. Similarly, 10–30% of the gynecological cancer survivors have shown radiation-induced symptoms such as urgency syndrome, leakage syndrome, excessive gas discharge, excessive mucus discharge, and blood discharge. The underlying mechanism is considered to be prolonged enhanced TGF signaling, which also causes latent fibrosis, and larger dosage per fraction may account for these higher rates. TGFβ combined with tumor necrosis factor-α cause inflammatory injury, which leads to increase in immune response and proliferation of fibroblasts at the site, leading additional tissue damage and fibrosis. Tissue fibrosis, a degenerative condition defined by enhanced mesenchymal cell proliferation into the interstitial space resulting in organ failure, promotes cancer growth and metastasis. The unregulated wound healing process, as well as the inflammatory response and tissue remodeling, is thought to be fibrosis initiating factors. Genes that promote disease progressions, such as CDKN2A, TP53, and SMAD4, are also implicated in tissue fibrosis because they contribute to the formation of the tumor microenvironment.,, Stromal cells, fibroblasts, and immune cells have a function in the tumor microenvironment. Fibroblast growth factor is secreted by stromal cells, which promotes cell proliferation and fibrosis. Cancer cachexia is a typical side effect of therapy, and the disease itself has a significant influence on the skeletal muscles. As a result of muscle regeneration, skeletal muscle injury can result in collagen and calcium depositions. Excessive calcium deposition may cause additional skeletal tissue injury.,,, The ADMA17/Notch signaling pathway, which are transmembrane receptors that govern fibroblast proliferation, is influenced by oxidative stress, resulting in dysregulation and profibrotic and inflammatory disorders.
| Chemotherapy And Its Role In Cancer-Related Fibrosis|| |
Chemotherapy is ineffective in differentiating healthy cells from malignant cells. This can cause tissue toxicity and tissue damage, resulting in fatigue, cognitive impairment, and GI symptoms such as cachexia and chemotherapy-induced diarrhea. Fibrosis is another typical adverse effect of cancer therapy, which usually comes in three stages. Cytokines are produced during the inflammatory phase, which attracts fibroblasts and other immune cells to the site of damage. This results in a proliferative phase in which the fibronectin matrix is generated together with deposits of collagen type III, establishing a new barrier. The remodeling phase is characterized by the accumulation of the extracellular matrix from local fibroblasts over a period of many weeks. As a result, when the wound healing mechanism is interrupted, reepithelialization is impeded, resulting in continual extracellular matrix enlargement and fibrosis., TGFβ levels are considerably higher in individuals receiving chemotherapy after bone marrow transplant. Chemotherapeutic drugs like bleomycin, doxorubicin, cyclophosphamide, and other platinum-based drugs are known to be associated with chemotherapy-related fibrosis. An animal study has found abnormalities in the left ventricular function and myocardial fibrosis after inducing doxorubicin indicating its role in promoting collagen formation and cardiac fibroblasts via the Neurokinin-1 receptor, resulting in cardiac muscle fibrosis independent of cardiomyocyte damage.,
| Surgery And Its Role In Cancer-Related Fibrosis|| |
Aspects such as age over 50, intraoperative high oxygen concentration, and surgical stress can all contribute to rapid respiratory impairment following surgery. Patients taking treatment for tumors such as lymphomas and soft tissue sarcoma are observed to develop left ventricular dysfunction and heart failure. There is an increase in collagen deposition as well as a considerable rise in cardiomyocyte apoptosis. Idiopathic pulmonary fibrosis, an abrupt respiratory impairment after anticancer treatment linked with interstitial pneumonia, affects 4–7.5% of lung cancer patients., According to a 2010 research, interstitial pulmonary fibrosis is seen in 16% of individuals who have had surgery. Chemotherapy and other adjuvant treatments raise the risk of developing idiopathic fibrosis.
| Role Of Physical Therapy Rehabilitation|| |
Cancer rehabilitation research has accelerated in the last decade, and treatment sequelae such as trismus, neuro-musculoskeletal dysfunction syndromes, fibrosis, speech and swallowing dysfunctions, upper limb and lower limb impairments, and sexual dysfunctions are of concern because they impact patients' quality of life. As a result, rehabilitation is necessary to enhance and preserve functional and physical abilities. Manual therapy and therapeutic modalities, speech and swallowing therapy, and vocational rehabilitation are all approaches to treating postcancer treatment problems.
Common consequences in head and neck cancers include trismus and shoulder dysfunction caused by spinal accessory nerve paralysis and radiation-induced fibrosis. Neck muscle fibrosis, trismus, neuropathy, physical deconditioning, myofascial restriction, frozen shoulder, and postural dysfunction must all be treated., Radiation-induced trismus is widespread in clinical settings, but no standard approach has been established due to a lack of research. Active range of motion exercises, manual stretching, and contract-relax antagonist-contract approaches have been demonstrated to improve incisional mouth opening in the short and long term. Therapeutic massage is also said to increase blood flow and relax the masticatory muscles, as well as exercises to break down myofascial adhesions and fibrosis, as well as jaw-mobilizing devices, can result in significant improvement in patients with radiation-induced trismus, particularly in the first 6 weeks.,, [Figure 2]a, [Figure 2]b, [Figure 2]c Temporomandibular joint mobilization and myofascial release to the neck muscles have demonstrated to be beneficial. For oral sub mucous fibrosis, techniques such as therapeutic ultrasound in conjunction with topical aloe-vera and turmeric gel administration and in combination with both are used. According to the literature, such therapies have no negative effects and have demonstrated benefits in mouth opening, tongue motions, mucosal flexibility, and changed oral sensation. Myofascial release, a manual therapy technique, has shown to enhance head and neck posture and have an influence on postural alignments. For axillary web syndrome which is commonly seen in breast cancer patients, moderate level of circular mobilization of the chest wall musculature including longitudinal tissue stretch of the cords is seen to help patients achieve an additional 10–15% of abduction range of motion, thoracic mobility, and decreased shoulder girdle pain and stiffness. Fibrosis of the vocal cords and discomfort can also cause speech and swallowing problems, as well as physical dysfunction, with up to 75% of cancer patients experiencing dysphagia after therapy. Radiation-induced adverse effects have been improved by myofascial release, physiotherapy exercises, external low-level laser, and speech and swallowing therapy.
|Figure 2: Demonstration of measurement of incisional mouth opening (a) pre-physiotherapy treatment, (b) post- physiotherapy treatment, and (c) demonstration of Myofascial Release Technique for Trismus|
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Posttreatment fibrosis is also noted in gynecological cancer patients. Dyspareunia is common which might have a psychosexual influence on the patient. Such individuals may exhibit sexual difficulty, body image concerns, pain, anxiety, sadness, and a variety of other medical and psychological symptoms. A physiotherapeutic strategy involving pelvic floor muscle exercises, biofeedback, manual therapy, home exercises, and counselling has been found to reduce sexual discomfort as well as physical and psychological symptoms in gynecological cancer survivors., Urinary incontinence is present in more than 80% of endometrial cancer patients with no past bouts of incontinence due to weak pelvic floor muscles caused by surgery and radiation., As a result, prerehabilitation is practical and crucial and has demonstrated to avoid incontinence and preserve strength even 1 month after radiation. A 30-min intervention of eight maximal voluntary low contractions of 6 s with 10 s rest, followed by eight 1-s maximal voluntary contractions followed by relaxation, and voluntary precontraction of the pelvic floor muscles to increase intraabdominal pressure before activities is highly recommended.
In GI cancers, patients may undergo extensive surgeries which may result in aforementioned posttreatment complications. There is evidence to suggest that such complications may be managed through preoperative physical therapy. In a multicenter trial, patients scheduled for major open abdominal surgery received a physical therapy intervention consisting of an information booklet, a 30-min physiotherapy education session, and a breathing exercise training session, as well as postoperatively early ambulation with no additional respiratory physiotherapy, all of who were followed for a year that concluded preoperative education and training to be beneficial to patients. Another analysis recommended preoperative exercise treatment for GI cancer patients, using treatments such as walking and aerobic training, as well as resistance training from prerehabilitation to 8 weeks postoperative period. Nutritional counselling and relaxation techniques are also key components of recovery. Such therapies have been demonstrated to improve patients' quality of life, functional ability, and physical well-being.,
| Conclusion|| |
Cancer and its therapies can have a detrimental impact on the body of the sufferer. As a result of the numerous physical and functional limitations, this might result in a lower quality of life. Pre- and postrehabilitation can thus aid in the prevention, management, and treatment of these adverse effects. An early intervention in form of physical therapy has shown to prove beneficial to most of the patients. However, delay in the referrals or ignorance by the patient or patient party may increase secondary comorbidities leading to impairment, disability, and decreased quality of life. As said, “Better Late than Never” physiotherapy either pre, early, or postcancer treatment shall always prove beneficial to this vulnerable population.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al
. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al
. ICMR-NCDIR-NCRP Investigator Group. Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Global Oncol 2020;6:1063-75.
Feng YL, Chen DQ, Vaziri ND, Guo Y, Zhao YY. Small molecule inhibitors of epithelial-mesenchymal transition for the treatment of cancer and fibrosis. Med Res Rev 2020;40:54-78.
Yarnold J, Brotons MC. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol 2010;97:149-61.
Rybinski B, Franco-Barraza J, Cukierman E. The wound healing, chronic fibrosis, and cancer progression triad. Physiol Genomics 2014;46:223-44.
Marichal T, Tsai M, Galli SJ. Mast cells: Potential positive and negative roles in tumor biology. Cancer Immunol Res 2013;1:269-79.
Schäfer M. Werner S. Cancer as an overhealing wound: An old hypothesis revisited. Nat Rev Mol Cell Biol 2008;9:628-38.
Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008;453:314-21.
Wang X, Zhang W, Sun X, Lin Y, Chen W. Cancerassociated fibroblasts induce epithelialmesenchymal transition through secreted cytokines in endometrial cancer cells. Oncol Lett 2018;15:5694-702.
López-Novoa JM, Nieto MA. Inflammation and EMT: An alliance towards organ fibrosis and cancer progression. EMBO Mol Med 2009;1:303-14.
Hecker L, Cheng J, Thannickal VJ. Targeting NOX enzymes in pulmonary fibrosis. Cell Mol Life Sci 2012;69:2365-71.
Roy K, Wu Y, Meitzler JL, Juhasz A, Liu H, Jiang G, et al
. NADPH oxidases and cancer. Clin Sci (Lond) 2015;128:863-75.
De Minicis S, Brenner DA. NOX in liver fibrosis. Arch Biochem Biophys 2007;462:266-72.
Ramírez-Amador V, Zambrano JG, Anaya-Saavedra G, Zentella-Dehesa A, Irigoyen-Camacho E, Meráz-Cruz N, et al
. TNF as marker of oral candidiasis, HSV infection, and mucositis onset during chemotherapy in leukemia patients. Oral Dis 2017;23:941-8.
Mun MS, Yap T, Alnuaimi AD, Adams GG, McCullough MJ. Oral candidal carriage in asymptomatic patients. Aust Dent J 2016;61:190-5.
Yang SF, Hsieh YS, Tsai CH, Chen YJ, Chang YC. Increased plasminogen activator inhibitor-1/tissue type plasminogen activator ratio in oral submucous fibrosis. Oral Dis 2007;13:234-8.
Khan I, Kumar N, Pant I, Narra S, Kondaiah P. Activation of TGF-β pathway by areca nut constituents: A possible cause of oral submucous fibrosis. PloS One 2012;7:e51806.
Ihn H. Pathogenesis of fibrosis: Role of TGF-β and CTGF. Curr Opin Rheumatol 2002;14:681-5.
Canney PA, Dean S. Transforming growth factor beta: A promotor of late connective tissue injury following radiotherapy? Br J Radiol 1990;63:620-3.
Nishioka AK, Ogawa YA, Hamada NO, Terashima MA, Inomata TA, Yoshida SH. Analysis of radiation pneumonitis and radiation-induced lung fibrosis in breast cancer patients after breast conservation treatment. Oncol Rep 1999;6:513-20.
Chang AR, Kim K, Kim HJ, Kim IH, Park CI, Jun YK. Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities. Int J Radiat Oncol Biol Phys 2006;65:1233-9.
Bibault JE, Prevost B, Dansin E, Mirabel X, Lacornerie T, Lartigau E. Image-guided robotic stereotactic radiation therapy with fiducial-free tumor tracking for lung cancer. Radiat Oncol 2012;7:102.
Hofsjö A, Bohm-Starke N, Blomgren B, Jahren H, Steineck G, Bergmark K. Radiotherapy-induced vaginal fibrosis in cervical cancer survivors. Acta Oncol 2017;56:661-6.
Steineck G, Skokic V, Sjöberg F, Bull C, Alevronta E, Dunberger G, et al
. Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors. PloS One 2017;12:e0171461.
Rübe CE, Uthe D, Schmid KW, Richter KD, Wessel J, Schuck A, et al
. Dose-dependent induction of transforming growth factor β (TGF-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation. Int J Radiat Oncol Biol Phys 2000;47:1033-42.
Fava LL, Kaulich M, Nigg EA, Santamaria A. Probing the in vivo
function of Mad1: C-Mad2 in the spindle assembly checkpoint. EMBO J 2011;30:3322-36.
Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, et al
. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 2010;142:531-43.
Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, et al
. IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 2004;119:285-98.
Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: Mediators, signaling, and metabolic pathways. Cell Metab 2012;16:153-66.
Mann CJ, Perdiguero E, Kharraz Y, Aguilar S, Pessina P, Serrano AL, et al
. Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle 2011;1:21.
Uezumi A, Ito T, Morikawa D, Shimizu N, Yoneda T, Segawa M, et al
. Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J Cell Sci 2011;124:3654-64.
Kharraz Y, Guerra J, Pessina P, Serrano AL, Muñoz-Cánoves P. Understanding the process of fibrosis in Duchenne muscular dystrophy. Biomed Res Int 2014;2014:965631.
Gissel H. The role of Ca2+in muscle cell damage. Ann N Y Acad Sci 2006;1066:166-80.
Kavian N, Marut W, Servettaz A, Nicco C, Chéreau C, Lemaréchal H, et al
. Reactive oxygen species-mediated killing of activated fibroblasts by arsenic trioxide ameliorates fibrosis in a murine model of systemic sclerosis. Arthritis Rheum 2012;64:3430-40.
Azzam EI, De Toledo SM, Harris AL, Ivanov V, Zhou H, Amundson SA, et al
. The ionizing radiation-induced bystander effect: Evidence, mechanism, and significance. Pathobiology of Cancer Regimen-Related Toxicities. New York, NY: Springer; 2013. p. 35-61.
Sempowski GD, Borrello MA, Blieden TM, Barth RK, Phipps RP. Fibroblast heterogeneity in the healing wound. Wound Repair Regen 1995;3:120-31.
Eckes B, Zigrino P, Kessler D, Holtkötter O, Shephard P, Mauch C, et al
. Fibroblast-matrix interactions in wound healing and fibrosis. Matrix Biol 2000;19:325-32.
Ueha S, Shand FH, Matsushima K. Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis. Front Immunol 2012;3:71.
Anscher MS, Peters WP, Reisenbichler H, Petros WP, Jirtle RL. Transforming growth factor β as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N Engl J Med 1993;328:1592-8.
Levick SP, Soto-Pantoja DR, Bi J, Hundley WG, Widiapradja A, Manteufel EJ, et al
. Doxorubicin-induced myocardial fibrosis involves the neurokinin-1 receptor and direct effects on cardiac fibroblasts. Heart Lung Circ 2019;28:1598-605.
Moudgil R, Yeh ET. Mechanisms of cardiotoxicity of cancer chemotherapeutic agents: Cardiomyopathy and beyond. Can J Cardiol 2016;32:863-70.e5.
Koizumi K, Hirata T, Hirai K, Mikami I, Okada D, Yamagishi S, et al
. Surgical treatment of lung cancer combined with interstitial pneumonia: The effect of surgical approach on postoperative acute exacerbation. Ann Thorac Cardiovasc Surg 2004;10:340-6.
Martinod E, Azorin JF, Sadoun D, Destable MD, Le Toumelin P, Longchampt E, et al
. Surgical resection of lung cancer in patients with underlying interstitial lung disease. Ann Thorac Surg 2002;74:1004-7.
Isobe K, Hata Y, Sakamoto S, Takai Y, Shibuya K, Homma S. Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology 2010;15:88-92.
Guru K, Manoor UK, Supe SS. A comprehensive review of head and neck cancer rehabilitation: Physical therapy perspectives. Indian J Palliat Care 2012;18:87-97.
] [Full text]
Glastonbury CM, Parker EE, Hoang JK. The postradiation neck: Evaluating response to treatment and recognizing complications. AJR Am J Roentgenol 2010;195:164-71.
Dall'Anese AP, Schultz K, Ribeiro KB, Carrara-de Angelis E. Early and long-term effects of physiotherapy for trismus in patients treated for oral and oropharyngeal cancer. Appl Cancer Res 2010;30:335-9.
Monisha N, Ganapathy D, Sheeba PS, Kanniappan N. Trismus: A review. J Pharm Res 2018;12:130-3.
Melchers LJ, Van Weert E, Beurskens CH, Reintsema H, Slagter AP, Roodenburg JL, et al
. Exercise adherence in patients with trismus due to head and neck oncology: A qualitative study into the use of the Therabite[INSIDE:1]. Int J Oral Maxillofac Surg 2009;38:947-54.
Gondivkar SM, Gadbail AR, Sarode SC, Gondivkar RS, Patil S, Gaikwad RN, et al
. Clinical efficacy of mouth exercising devices in oral submucous fibrosis: A systematic review. J Oral Biol Craniofac Res 2020;10:315-20.
Calixtre LB, Moreira RF, Franchini GH, Alburquerque-Sendín F, Oliveira AB. Manual therapy for the management of pain and limited range of motion in subjects with signs and symptoms of temporomandibular disorder: A systematic review of randomised controlled trials. J Oral Rehabil 2015;42:847-61.
Meshram M, Bhowate RR, Madke B, Sune R. Evaluation of the effect of ultrasound physiotherapy interventions in combination with local application of aloe-vera and turmeric gel in the management of oral submucous fibrosis. J Dent Investigat 2018;1:16-33.
Dixey J, Purohit K, Greenfield DM. Myofascial release and muscle retraining for dropped head syndrome attributed to radiation fibrosis in hodgkin lymphoma: A case series. Rehabil Oncol 2017;35:188-94.
Fourie WJ, Robb KA. Physiotherapy management of axillary web syndrome following breast cancer treatment: Discussing the use of soft tissue techniques. Physiotherapy 2009;95:314-20.
Sroussi HY, Epstein JB, Bensadoun RJ, Saunders DP, Lalla RV, Migliorati CA, et al
. Common oral complications of head and neck cancer radiation therapy: Mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med 2017;6:2918-31.
Pattanshetty D, Mascarenhas K, Dias K. Shaker's exercise rehabilitation in head and neck cancer patients – A clinical trial. J Med Sci Clin Res 2017;5:27131-9.
Cyr MP, Dumoulin C, Bessette P, Pina A, Gotlieb WH, Lapointe-Milot K, et al
. A prospective single-arm study evaluating the effects of a multimodal physical therapy intervention on psychosexual outcomes in women with dyspareunia after gynecologic cancer. J Sex Med 2021;18:946-54.
Cyr MP, Dumoulin C, Bessette P, Pina A, Gotlieb WH, Lapointe-Milot K, et al
. Characterizing pelvic floor muscle function and morphometry in survivors of gynecological cancer who have dyspareunia: A comparative cross-sectional study. Phys Ther 2021;101:pzab042.
Bernard S, Moffet H, Plante M, Ouellet MP, Leblond J, Dumoulin C. Pelvic-floor properties in women reporting urinary incontinence after surgery and radiotherapy for endometrial cancer. Phys Ther 2017;97:438-48.
Ramaseshan AS, Felton J, Roque D, Rao G, Shipper AG, Sanses TV. Pelvic floor disorders in women with gynecologic malignancies: A systematic review. Int Urogynecol J 2018;29:459-76.
Sacomori C, Araya-Castro P, Diaz-Guerrero P, Ferrada IA, Martínez-Varas AC, Zomkowski K. Pre-rehabilitation of the pelvic floor before radiation therapy for cervical cancer: A pilot study. Int Urogynecol J 2020;31:2411-8.
Boden I, Skinner EH, Browning L, Reeve J, Anderson L, Hill C, et al
. Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: Pragmatic, double blinded, multicentre randomised controlled trial. BMJ 2018;360:j5916.
Vermillion SA, James A, Dorrell RD, Brubaker P, Mihalko SL, Hill AR, et al
. Preoperative exercise therapy for gastrointestinal cancer patients: A systematic review. Syst Rev 2018;7:103.
Mancini ML, Sonis ST. Mechanisms of cellular fibrosis associated with cancer regimen-related toxicities. Front Pharmacol 2014;5:51.
[Figure 1], [Figure 2]