Editor-in-Chief Emeritus Pick of Papers
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For each issue of Radiotherapy and Oncology, the Editor-in-Chief Emeritus Jens Overgaard, picks his favourite papers.
- A viable alternative for surgery to treat early stage non-small-cell lung cancer is stereotactic body radiation therapy (SBRT) [1,2]. The dose distributions need to be highly conformal around the target to ensure coverage, while sparing adjacent organs at risk (OARs) . Although Intensity Modulated Radiation Therapy (IMRT) produces conformal dose distributions, Volumetric Modulated Arc Therapy (VMAT) can in some cases spare even more tissue with equal target coverage . On C-arm linacs, VMAT typically reduces delivery times when combined with high-dose rate flattening-filter free beams .
- Any cancer that can metastasise to the spinal column or within the epidural space has the potential to cause cord compression. It is well recognised that prostate, breast and lung cancers often metastasise to the spine and these typically make up 45–60% of metastatic spinal cord compression (MSCC) cases . Other less frequent tumours include renal cell carcinoma, multiple myeloma, sarcoma, colorectal cancers, non-Hodgkin lymphoma, and cancers of unknown primary. Table 1 is a representation of tumours causing MSCC, taken from a large systematic review , however this should be viewed with caution as papers included within the systematic review may have excluded certain cancer types.
- After liver and lungs, bone is the third most common metastatic site . Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer . Introduction of effective systemic treatment in many cancers has prolonged patients’ survival, including those with bone metastases.
- Surface Guided Radiation Therapy (SGRT) is a relatively recent technology that was added to existing image guidance systems. SGRT typically uses visible structured light, stereo-vision systems, time-of-flight systems, or laser scanners to image the surface of a patient with high temporal and spatial resolution without additional radiation dose [1,2].
- Myeloablative Total Body Irradiation (TBI) has long been a cornerstone of the conditioning for hematopoietic stem cell transplantation (HSCT) in children , but is associated with considerable late effects [2–6]. Currently, use of TBI is mainly indicated in allogeneic HSCT for high-risk hematologic malignancy [7–13]. Fractionated TBI (fTBI) is standard for pediatric radiotherapy centers, but practices vary [14,15]. While most centers perform conventional TBI, several institutions have introduced highly conformal TBI techniques or Total Marrow Irradiation (TMI), Total Lymphoid Irradiation (TLI), and Total Marrow and Lymphoid Irradiation (TMLI) [16–19].
- Two-thirds of the central nervous system tumors, the most common solid neoplasm in children, occur in the posterior fossa. With improvements in surgical technologies, chemotherapy and radiotherapy protocols over the past decades, the 5-year survival rate for children with a posterior fossa tumor (PFT) have increased for the main histological types of tumors diagnosed during childhood. The survival rate is 90% for astrocytoma (30% of PFT), 60% for ependymoma (10% of PFT), and 80% for medulloblastoma (40% of PFT).
- Irradiation with protons has two important advantages over irradiation with photons. Firstly, proton therapy offers the possibility of sparing normal tissue much better than conventional radiotherapy, due to its physical dose profile, while maintaining the same dose in the tumour and secondly, proton irradiation is biologically more effective than photon irradiation . Therefore, dose prescription in clinics uses the relative biological effectiveness (RBE) to convert the absorbed dose to an RBE-weighted dose corresponding to an isoeffective photon dose.
- Lung cancer is the most common cancer worldwide with an incidence of 2.2 million reported in 2020 . Radical radiotherapy (RT) is used to treat locally advanced non-small cell lung cancer (NSCLC), early-stage NSCLC not suitable for surgery, and limited stage small cell lung cancer (SCLC). Incidental exposure of the heart is unavoidable in most patients, and this may increase the risk of cardiac disease including ischaemic heart disease, heart failure, valvular heart disease, pericardial disease, and conduction system abnormalities [2,3].
- The internal mammary nodes (IMN) receive lymphatic drainage from all quadrants of the breast [1–5], with predominant drainage to IMNs in case of inner quadrant and deeply located nonpalpable tumours . Among patients who have pathologically node-negative axillary disease, up to 10% may have IMN tumour involvement, which increases to almost 40% in case of involved positive axillary nodes [1–6]. IMN dissection was not shown to provide survival benefit . For many years thereafter, elective IMN irradiation was controversial, as data were conflicting for disease outcome benefits vs potential detrimental effects of radiation therapy (RT) [7,8].
- Several studies suggest that Diversity, Equity and Inclusion (DEI) in the medical workforce may improve patient care and innovation [1–3]. Diversity involves being mindful of differences such as age, gender identity, ethnicity, religion, sexual orientation, or disability status . Equity means that everyone receives fair treatment and has equal access to opportunities, while inclusion of diverse individuals in the workplace is achieved by providing support, access to information, a sense of belonging and job security [4,5].
- Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) are currently treated with postoperative radio-chemotherapy (PORT-C) or primary radio-chemotherapy. While the inclusion of chemotherapy improved the outcome significantly [1,2], treatment response is still heterogeneous. To further individualize therapy in order to improve treatment response, additional biomarkers need to be identified and applied in personalized treatment escalation or de-escalation strategies [3,4].
- Anal cancer (AC) is an uncommon disease, yet over the past decade the incidence of anal cancer has increased by 2.2% each year . Development of anal cancer is strongly associated with the presence of human papilloma virus (HPV) infection, with >90% of anal cancers directly attributed to HPV .
- The DBCG 82bc randomized trial recruited between 1982 and 1990 3083 patients in a clinical trial to address the importance of postmastectomy radiotherapy (PMRT) to high-risk breast cancer patients who also received adjuvant systemic treatment [1,2]. The trial was initiated at a time where the role of local tumor control was heavily debated in the light of the potential importance of controlling a nidus for subsequent disseminated disease. The study therefore challenged the Alternative Hypothesis formulated by the late Bernard Fisher as an alternative to the original Halstedian Hypothesis, which states that tumors spread in an orderly defined manner, and that the extent and nuances of the loco-regional treatment are the dominant factors influencing patient outcome .
- One of the common treatment modalities for prostate cancer (PCa) is external-beam radiotherapy . Considering the relatively low alpha/beta ratio for PCa [2,3], hypofractionation could yield higher tumour control rates with acceptable genitourinary and gastrointestinal toxicity rates . Dose-escalation has shown improved treatment outcomes  and the use of modern image-guidance techniques, like fiducial markers, have lowered the margin needed around the prostate and thereby lowered side effects [6,7].
- With annual incidence of 0.5 per 100,000, anal cancer accounts for <3% of lower gastrointestinal tract malignancies [1,2]. It is more common in immunocompromised patients and smokers . Rise of incidence over past decades  can be attributed to the increased prevalence of HPV infection which is the most important cause [3,5]. Abdominoperineal resection was the main treatment in the past, but resulted in suboptimal locoregional control and high morbidity due to sphincter loss . Following encouraging first experience with chemoradiation [7,8], its effectiveness was confirmed by several retrospective and phase II studies [9–13].
- Ledderhose disease, also called plantar fibromatosis, is a benign hyperproliferative disease of the plantar fascia and was first described by Georg Ledderhose in 1897 . The disease is characterized by the formation of nodules and/or cords under the sole of the foot, often located on the medial and central bands of the plantar fascia [2–4]. These nodules can be asymptomatic, though patients may experience some discomfort . The discomfort can vary in intensity from slight tenderness to severe pain and can appear during activity as well as while at rest.
- Radiotherapy is used with curative-intent in ∼50% of prostate cancer cases , but late toxicities adversely impact quality-of-life. Hemorrhagic radiation cystitis, defined by gross hematuria, can be a severe and life-threatening complication . The biologic mechanisms are poorly understood, hindering identification of molecular targets for protection or mitigation.
- Prostate brachytherapy is a highly effective treatment for localised prostate cancer in patients who have no evidence of metastases. It is indicated in two settings:
- Anal squamous cell carcinoma (ASCC) is a rare tumor entity with a steady rise in incidence . Primary chemoradiotherapy (CRT) with 5-fluorouracil and mitomycin C (5-FU/MMC) remains the standard treatment for localized disease since the introduction of this treatment approach by Nigro et al. in the 1980s . Radical surgery with abdominoperineal resection and a permanent colostomy is now reserved for patients with locally persistent or recurrent disease after CRT. The addition of sequential chemotherapy, either prior to or following primary CRT, or dose escalation of radiotherapy was tested in several randomized trials, but failed to improve oncological results [3–5].
- A patient with a cutaneous lymphoma was treated on the same day for 2 distinct tumors using a 15 Gy single electron dose given in a dose rate of 0.08 Gy/second versus 166 Gy/second. Comparing the two treatments, there was no difference for acute reactions, late effects at 2 years and tumor control.
- Compared to paediatric patients, indications for proton therapy (PT) for adult patients are less acknowledged . Although radiation of intra-ocular tumours and chordoma/chondrosarcoma of the skull base are currently regarded as standard indications for adult patients in virtually all countries, there are major differences regarding patient selection for PT across European countries and even between centres in the same country [2–4]. This is especially true for adult patients who would normally be treated with photon therapy but may benefit from PT because of more favourable dose distributions.
- Worldwide, approximately 710,000 patients are diagnosed annually with head and neck cancer (HNC) [1,2].
- Surgery or radiotherapy (RT), and in more advanced tumours a combination of the two modalities, is the standard approach for the curatively intended treatment of oral cavity squamous cell carcinoma (OCSCC). A long-standing controversy has been the order of sequence for surgery and RT; pre- or postoperative RT as to whether there is any advantage of this order in relation to tumour control, survival, toxicity, and functional outcome. There is a lack of randomised trials to settle this question. An early RTOG study  found an improvement in local control for postoperative compared with preoperative RT in patients with locally advanced head and neck SCC, but no differences in overall survival (OS) or morbidity.
- Uveal melanoma (UM) represents the second most common form of melanoma and the most common primary intraocular tumor with an occurrence, in both the U.S. and Europe, of about 5–7.5 cases per million people per year [1–4].
- Investigators have recently reported significant negative associations between heart irradiation and overall survival (OS) following radical radiotherapy (RT) for non-small cell lung cancer (NSCLC) [1–8]. We analysed OS in a cohort of patients, ‘IDEAL-6′, treated in the IDEAL-CRT phase 1/2 trial of isotoxically dose-escalated RT for locally-advanced NSCLC given in 30 fractions over 6 weeks concurrent with chemotherapy [8,9]. OS was significantly associated with one principal component (PC) of patients’ heart dose-distributions, which described fractional heart volumes receiving equivalent doses in 2 Gy fractions (EQD2) of 64–73 Gy (α/β = 3 Gy ), delivered largely to the left atrial (LA) wall.