History Of External Beam Radiotherapy Research Articles

External Beam Radiotherapy in Western Africa: 1969–2019

AimsWe describe the absolute and per capita numbers of megavoltage radiotherapy machines (MVMs) in Western Africa from 1969 to 2019. Materials and methodsWestern Africa was defined in accordance with the United Nations' delineation and inclusive of 16 countries. A literature search for publications detailing the number of cobalt-60 machines (COs) and linear accelerators (LINACs) in radiotherapy centres was carried out. Population data from the World Bank Group and crude cancer rates from the International Agency for Research on Cancer were used to calculate ratios of million persons per MVM and MVMs per 1000 cancer cases. ResultsThe numbers of MVMs in Western Africa in 1969, 1979, 1989, 1999 and 2009 were zero, two, three, six and nine, respectively. In 2019 there were 22 MVMs distributed across Ghana (five), Côte d’Ivoire (two), Mali (one), Mauritania (two), Nigeria (nine) and Senegal (three). Nine countries (56.3%) had no history of external beam radiotherapy (EBRT). The largest increase in absolute EBRT capacity occurred from 2017 to 2019, during which 13 MVMs were commissioned. The largest decrease in EBRT capacity occurred from 2015 to 2017, during which four LINACs and three COs were rendered non-operational. The ratio of million persons per MVM improved from 67.0 in 1979 to 17.8 in 2019. As of 2019, there was 0.09 MVM per 1000 cancer cases. ConclusionsWestern African nations have experienced an increase in the absolute number of MVMs and per capita radiotherapy capacity during the last 50 years, especially in the last decade. As non-functional LINACs contributed to a temporary decline in the EBRT infrastructure, dual use of CO/LINAC technologies may act to promote the availability of EBRT treatment in centres with capacity for multiple MVMs.

External Beam Radiotherapy in West Africa: 1979 - 2019

External beam radiotherapy (EBRT) commenced in West Africa with the provision of Cobalt-60 teletherapy (CO) treatment at Lagos University Teaching Hospital, Nigeria in 1973. No analysis of the trend in EBRT capacity specific to this region, including the installation of linear accelerators (LINACs), has been performed to date. The purpose of this study is to present the number of megavoltage units (MVUs) in West Africa from 1979 to 2019. West Africa was defined in accordance with the United Nations delineation and inclusive of Benin, Burkina Faso, Cabo Verde, Cote d’Ivoire, The Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, and Togo. A literature search for publications detailing the number of MVUs in West African radiotherapy centers was performed, and extracted MVU data were confirmed using the Directory of Radiotherapy Centers (DIRAC). Population data were obtained from the Word Bank Group and used to determine the number of MVUs per 100 million persons. Nine of 16 (56.3%) West African countries have no history of EBRT, and one country (Liberia) lost its treatment capacity. The number of operating MVUs in 1979, 1989, 1999, 2009, and 2019 were 1, 2, 5, 8, and 22, respectively. Five centers currently house 2 MVUs, including 2 centers which offer both CO and LINAC treatments. The largest absolute decrease EBRT capacity occurred from 2014 to 2017 during which 1 CO unit was decommissioned and 6 MVUs (1 CO unit and 5 LINACs) were deemed non-functional. The largest absolute increase in EBRT capacity occurred from 2017 to 2019. In this interval, LINACs were installed in Cote d’Ivoire (2), Ghana (2), Mauritania (1), and Senegal (3). In Nigeria, 2 CO units and 5 LINACs were either commissioned or rehabilitated. When MVUs known to be non-functional were excluded, the numbers of MVUs per 100 million persons were 1.3 in 1979, 1.1 in 1989, 2.2 in 1999, 2.7 in 2009, and 5.6 in 2019. West African nations have experienced an increase in the absolute number of MVUs installed in public and private centers in the last 40 years. However, the MVUs-to-persons ratio is still well below the ideal ratio of 1 MVU per 250,000 persons recommended by the International Atomic Energy Agency. As non-functional LINACs contributed to a marked decline in the EBRT infrastructure of the region from 2014 to 2017, a strategy of dual use of CO/LINAC technologies may act to ensure the availability EBRT treatment in centers with capacity for multiple MVUs.

Functional outcomes of artificial urinary sphincter implantation with distal bulbar double cuff in men with and without a history of external beam radiotherapy: an analysis of a prospective database

ObjectivesTo analyse functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation with a distal bulbar double cuff (DC) for the treatment of stress urinary incontinence (SUI) in men with and without a history of external beam radiotherapy (RT).Patients and MethodsData of all patients undergoing AUS implantation with a distal bulbar DC (DC‐AUS) were collected prospectively from 2009 to 2015. Indications for DC implantation were based on urethral risk factors in terms of RT and previous proximal bulbar urethral interventions including, endoscopic or open surgery for urethral stricture or SUI. Implantation was carried out to a standardised protocol. Activation of the AUS was performed 6 weeks after implantation. Further follow‐up (FU) included pad test, uroflowmetry, post‐void residual urine measurements, radiography, and a standardised questionnaire. Continence and complication rates were compared between patients with a history of RT and non‐RT patients. Explantation‐free survival was estimated using Kaplan–Meier curves and the log‐rank test. Firth's penalized Cox‐regression analyses were performed to analyse proportional hazard ratios for explantation.ResultsIn all, 150 men (median age 70 years, interquartile range [IQR] 66–74) after DC‐AUS implantation were available for analysis. Overall, 73 men (48.7%) had a history of RT. The median (IQR) FU was 24 (7.25–36) months. Baseline clinical characteristics only differed regarding previous open SUI surgery (P = 0.016). Social and objective continence was achieved in 94.8% and 84.3% of all patients treated by implantation of a DC‐AUS, respectively. Between the RT and non‐RT patients there were no statistically significant differences in continence rates [social continence: 100% vs 90.2% (P = 0.194); objective continence: 87% vs 82% (P = 0.877)]. For complications rates there were no significant differences between RT and non‐RT patients after DC‐AUS implantation [infection (P = 0.09), erosion (P = 0.31), mechanical failures (P = 0.14)]. According to Kaplan–Meier analysis explantation rates in patients with a history of RT (26.0%) vs non‐RT patients (20.8%), estimated explantation‐free survival, and AUS durability, did not differ significantly (log‐rank P = 0.219).ConclusionOur data from a large institutional series indicate DC‐AUS implantation to be an effective and safe treatment strategy in men with SUI and a history of RT.

Three-dimensional-printed individual template-guided 125I seed implantation for the cervical lymph node metastasis: A dosimetric and security study.

The objective of this study is to evaluate the dosimetric accuracy and pathway safety of the three-dimensional (3D)-printed individual template-guided 125I seed implantation for the treatment of cervical lymph node metastasis. A total of 15 consecutive patients with cervical lymph node metastasis were enrolled during September 2015-July 2017 (12 patients had a history of external beam radiotherapy, with the mean dose of 63 Gy), who undergone radioactive seed implantation guided by the 3D-printed individual template. The preplan was completed based on contrast-enhanced computed tomography images, and then, the 3D-printed individual template was printed according to the preplan. After the operation, the real-time dose verification was completed: the D90 was ranged from 60 to 113 Gy with median of 93 Gy and the number of seeds was ranged from 21 to 76 with median of 53. To observe the intraoperative complications and postoperative complications in 3 days, we collected and compared the deviation of the number of seeds, target volume, and dosimetric parameters (D90, V90, V100, and V150) between preplan and postoperative plan. Intraoperatively, each template was observed to exactly fit and lock on the lamina, and the operation was successfully completed. No intraoperative complications and postoperative complications were observed in 3 days. There was no significant difference in P values between the two groups for all the parameters (P > 0.05). The 3D-printed individual template-guided 125I seed implantation for the cervical lymph node metastasis has not only reduced the dosimetric differences between pre- and postplan but also lowered the difficulty of puncture, indicating that it was a safe and accurate guidance approach.

The impact of bladder neck sparing on urinary continence during laparoscopic radical prostatectomy; Results from a high volume centre.

To evaluate the effects of bladder neck reconstruction techniques on early continence after laparoscopic radical prostatectomy (LRP). This non-randomized retrospective study analyzed prospectively collected data concerning LRP. In total, 3107 patients underwent LRP between March 1999 and December 2016. Exclusion criteria were preoperative urinary incontinence, previous history of external beam radiotherapy, co-morbities which may affect urinary continence such as diabetes mellitus and/or neurogenic disorders, irregular followup, and follow-up shorter than 24 months. All patients were divided into one of three groups, posterior reconstruction being performed in Group 1 (n = 112), anterior reconstruction in Group 2 (n = 762), and bladder neck sparing (BNS) in Group 3 (n = 987). Demographic and pre-, peri-, and postoperative data were collected. Multivariate analyses were performed to determine factors affecting early continence after LRP. 1861 patients were enrolled in the study. The mean follow-up period was 48.12 ± 29.8 months, and subjects' mean age was 63.6 ± 6.2 years. There was no significant difference among the groups in terms of demographic or preoperative data. Postoperative data, including oncological outcomes, were similar among the groups. The level of early continence was higher in Group 3 than in the other groups (p < 0.001). Multivariate analyses identified BNS and age as parameters significantly affecting early continence levels after LRP (p < 0.001 and p < 0.001, respectively). Bladder neck reconstruction provided less earlier continence than BNS.

Development of a Nomogram for Predicting Severe Neutropenia Associated With Docetaxel-Based Chemotherapy in Patients With Castration-Resistant Prostate Cancer

BackgroundNeutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). Patients and MethodsThis study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. ResultsSixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. ConclusionAge and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy.

Dual malignancies in the setting of differentiated thyroid carcinoma

The primary objective of the study was to assess the risk for second primary malignancy after radioiodine treatment for differentiated thyroid carcinoma (DTC). Other objectives were to study the different variables associated with the occurrence of synchronous or metachronous dual malignancies in association with DTC. The patient population studied comprised patients with histopathologically proven DTC referred for radioactive iodine treatment after thyroidectomy followed up at a single centre during the period from January 1963 to March 2011. The data collected were analysed with respect to different variables associated with two primary tumours in the setting of DTC. Out of the total 8614 patients studied from 1963 to March 2011, 44 dual malignancies in association with DTC were detected, showing a prevalence rate of 0.5%. The most common site of second primary malignancy was the head and neck (H&N) in men and the breast in women. Of the 44 dual malignancies, 18 were synchronous in nature and 26 were metachronous. In the metachronous group, thyroid carcinoma was the first primary malignancy in only 5/26 patients, whereas the remaining 21 patients had thyroid carcinoma as the second primary malignancy. In 5/26 patients in whom carcinoma of the thyroid was the first primary malignancy, the second primary malignancy was breast carcinoma in two cases, renal cell carcinoma in one case, colorectal carcinoma in one case and metastatic NET of unknown primary in one case. All these five patients received radioiodine treatment with different activities. In 21/26 patients in whom thyroid carcinoma was the second primary malignancy, the most common first primary malignancy comprised H&N tumours. In this group, 12 patients had a history of external beam radiotherapy (EBRT). Among synchronous malignancies (18/44 patients), H&N tumours were the most commonly associated. There was no significant risk for second primary malignancy after radioactive iodine treatment in patients with DTC. There is increased risk for thyroid malignancy after EBRT delivered for other primary tumours, especially in children. Hence, any thyroid abnormality on long-term follow-up of patients after EBRT for other tumours should be considered carefully. H&N malignancies are the most common synchronous, metachronous and overall associated second malignancy with thyroid carcinoma.

Implantation du sphincter urinaire artificiel AMS 800 : la voie péno-scrotale est-elle une alternative à la voie périnéale ?

To compare the short-term results of penoscrotal and perineal artificial urinary sphincter implantation. From May 2005 to February 2007, 37 artificial urinary sphincters were implanted successively, via a penoscrotal approach in 16 cases and via a perineal approach in 21 cases. Incontinence was secondary to prostate surgery (n=36) and pelvic trauma (n=1). Seventeen patients had a history of external beam radiotherapy. The times and modalities of activation of the sphincter were identical in the two groups. The mean age of the patients, the mean operating time, the mean catheterization duration, the mean hospital stay and the mean postoperative follow-up were equivalent in the two groups. Six urethral erosions (37.5%) and one scrotal erosion due to the pump (6.6%) were observed in the penoscrotal group and infection of the sphincter in two patients (9.5%) and pump migration in another two patients (9.5%), but no urethral erosions were observed in the perineal group. The success rate without revision was 56% in the penoscrotal group and 71.5% in the perineal group. The perineal approach is the reference incision, as the penoscrotal approach is associated with a high rate of erosion. The penoscrotal urethral approach can constitute an alternative when the bulbar urethra cannot be used.

Skull Base Osteomyelitis

Skull base osteomyelitis may develop as a complication of paranasal sinusitis or other regional infectious process or as an unfortunate sequelae of iatrogenic injury or trauma. Afflicted patients generally have some form of systemic immunocompromise, most often diabetes, or a history of external beam radiotherapy for a head and neck malignancy with the radiation portal encompassing the area of the skull base. Before the era of systemic antimicrobial therapy, skull base osteomyelitis was almost universally fatal. Acute osteomyelitis often results in rapid lytic destruction of the skull base bone commonly associated with cranial nerve palsy/paralysis, and rarely, with craniovertebral instability and intracranial abscess formation. It may or may not be associated with a deep fascial, orbital or intracranial soft tissue component. Chronic osteomyelitis, as seen in granulomatous conditions, is often much more indolent and slowly progressive. Patients may still exhibit cranial nerve palsies, albeit usually more slowly. As such, they are often able to compensate for these losses over time and hence often delay their clinical presentation. In contradistinction to malignant otitis externa (otologic skull base osteomyelitis), nonotologic skull base osteomyelitis may pose a significant diagnostic clinical challenge. There are no pathognomic findings on clinical or radiographic examination which confirm skull base osteomyelitis. Tissue diagnosis is the key to both diagnosis and management of this rare entity. Preoperative CT or MRI-guided fine needle aspiration of accessible lesions is warranted for all skull base lesions. Unfortunately, this is not feasible in many cases due to inaccessibility. Thus, advanced open and/or endoscopic craniofacial approaches are required to allow for safe exposure of the affected areas. Preoperatively, it may not be possible to differentiate infectious from neoplastic entities that can present in a similar fashion. Once access has been achieved, confirmatory biopsy should be sent for pathologic analysis. If osteomyelitis is confirmed, then aggressive surgical debridement of grossly affected bone, preserving neurovascular anatomy whenever possible, followed by culturedriven systemic antibiotic therapy (generally for 6 weeks) is the mainstay of treatment. Initial or suspected nonotologic osteomyelitis should be treated empirically to provide coverage for Staphylococcus aureus. This is in contradistinction again to otologic osteomyelitis where empiric coverage for Pseudomonas aeruginosa should be provided. Cultures should always be sent to evaluate for possible fungal and tuberculosis pathologies as well. Serial gallium scans may be useful to follow these patients postoperatively as a marker of response to treatment. Serial CT and MRI scanning seems to be less useful in this regard. With aggressive surgical debridement facilitated by the broad exposure provided by modern craniofacial approaches, followed by tissue-guided systemic antimicrobial therapy, one can anticipate resolution of the progressive radiographic findings, and often times, note reversal or improvement of neural deficits (especially those of recent onset). Refractory cases and those arising in a radiated field may benefit from the adjunctive use of hyperbaric oxygen therapy (minimum of 30 dives). The major difficulty encountered by the clinician treating this patient population remains that of establishing a sound diagnosis and differentiating this lesion from a neoplastic process.

Female urethral strictures: successful management with long‐term clean intermittent catheterization after urethral dilatation

To report our experience in the diagnosis and treatment of urethral stricture in women. A retrospective review of records and video-urodynamics identified women treated for urethral stricture between 1999 and 2004 at one institution by one surgeon. Urethral stricture was defined as a fixed anatomical narrowing between the bladder neck and distal urethra of <14 F preventing catheterization, and the diagnosis was confirmed by cysto-urethroscopy, and/or video-urodynamics. Women with a history of external beam radiotherapy to the pelvis, or of gynaecological, urethral or bladder malignancy, were excluded, and the women had a urethral biopsy to exclude a malignant cause of the stricture. Initial treatment consisted of urethral dilatation to > or = 30 F. After a period of indwelling catheterization, the women were placed on clean intermittent self-catheterization (CISC) at least once daily, and monitored every 3-6 months. At each follow-up, the urethra was catheterized to exclude recurrence. American Urological Association (AUA) symptom scores were obtained at presentation and at the initial 3 month follow-up. Seven women met the criteria for urethral stricture, and were followed for a mean (range) of 21 (6-34) months. All were initially maintained on daily CISC, and some were gradually reduced to weekly CISC for the duration of follow-up. No patient had a recurrent stricture while on CISC, and none has had a urethral reconstruction to manage their condition. AUA symptom scores improved in all of the women by a mean of 10.7 points. No complications related to catheterization were noted. Urethral stricture is rare in women. Long-term CISC in these women is safe and effective, and can avoid the need for major reconstructive surgery.

Intraoperative ultrasonography improves identification of recurrent thyroid cancer

Background. Surgical resection is the only curative treatment option for locoregional recurrence of well-differentiated thyroid cancer that does not trap radioiodine. We hypothesized that intraoperative ultrasonography would aid in the localization of recurrent thyroid cancer and would enhance the ability to perform a complete resection. Methods. Between June 2000 and October 2001, 13 patients with recurrent, scan-negative, papillary thyroid cancer were explored by using intraoperative ultrasonography. Results. All patients had identification and resection of recurrent papillary thyroid cancer. Eleven patients had a complete resection, and 2 patients had incomplete resection as a result of local invasion. Ultrasound was required for identification of tumor in 7 patients and included all patients with a history of external beam radiotherapy. In 6 of these 7 patients, the tumor was paratracheal or invasive into the trachea or thyroid cartilage. In 11 patients with detectable serum thyroglobulin preoperatively, the level demonstrated a decline in 10 patients and became undetectable in 7 patients. Conclusions. Intraoperative ultrasonography is a useful method to identify nonpalpable, locoregional recurrences of thyroid cancer. Ultrasound was particularly helpful in patients who had previous external beam radiotherapy and in the identification of tumor nodules of 20 mm or less that were invasive or adherent to the airway. (Surgery 2002;132:924-9.)

Complications of cystectomy in patients with a history of pelvic radiation

Objectives. To compare the complications occurring during the first year of follow-up after radical cystectomy in two groups, one with and one without a history of pelvic radiation. Radical cystectomy and urinary diversion is the treatment of choice for invasive bladder cancer. Methods. One hundred ninety-four cystectomies were performed between January 1995 and June 2000 by a single surgeon. Twenty-three patients were identified with a history of external beam radiotherapy to the pelvis (EBRT group), and 23 additional patients without a history of pelvic radiation were randomly selected to serve as the control group. Results. Although the overall risk of having a complication was not statistically different in the EBRT group (48%) than in the control group (30%; P = 0.183), complications directly related to surgery were higher in the EBRT group than in the control group (48% versus 26%; P = 0.045). The patients in the EBRT group were more likely to require an invasive procedure (39% versus 9%; P = 0.018). In addition, 5 (22%) of 23 patients in the EBRT group had a symptomatic fluid collection, which was diagnosed as a urine leak (n = 2) or an abdominal abscess (n = 3). In contrast, no patient in the control group developed a symptomatic fluid collection. Conclusions. Cystectomy after pelvic radiation is associated with acceptable morbidity; however, compared with cystectomy performed in a nonirradiated pelvis, the risk of complications that will require invasive intervention is increased. A history of prior pelvic radiation significantly increases the risk of a symptomatic fluid collection.

Radiotherapy with heavy ions: radiobiology, clinical indications and experience at GSI, Darmstadt.

In the history of external beam radiotherapy, the trend for a better conformation as well as for a higher biological efficiency has been the driving force for the improvement of clinical results. However, these two goals had to be followed with separate types of radiation, i.e. photons and neutrons, and could not be combined. For the first time being, beams of heavy ions like carbon offer the possibility to combine both advantageous properties: better targeting and higher biological efficiency. Particle beams have an inverse depth dose profile, with a maximum dose in the deep seated tumor, a finite range, small lateral scattering, and a drastically increased biological efficiency in the tumor. These properties maximize the deletion effects on tumor cells. In addition, particle beams can be directed precisely in the limit of one or two millimeters, and can be monitored using positron emission tomography (PET) with the same precision. In the following paper the conditions are given that are necessary to translate these properties into clinical routine.