In this retrospective study, we analyzed changes in the therapeutic management of inpatients with CC and HNC across 14 German university hospitals following the lockdown announcement on March 16, 2020, in Germany [21]. A significant decrease in performed radiotherapy fractions for malignant neoplasms of the cervix uteri was observed across all participating sites in 2020 in the 20 weeks following the lockdown announcement on March 16, 2020, in Germany to August 2, 2020, compared to the average of the two previous years. This effect was especially driven by a reduction of Megavoltage radiation therapy (OPS 8‑522, 8‑523), whereas no differences were observed for brachytherapy (OPS 8‑524, 8‑525). Notably, even though on April 28, 2020, the German Federal Ministry of Health announced the gradual reactivation of hospital capacity for elective treatments from May onwards [20], the observed reduction was even more pronounced when analyzing the time period from May 4, 2020, to August 2, 2020, in more detail. These numbers are in accordance with our analysis of related hospital admissions.
The observed decrease in case numbers for CC with associated radiotherapy goes hand in hand with little, non-significant changes in hospitalizations treated surgically. In light of the restricted operating theater and intensive care capacity, the unlikely finding of a decrease is surprising but may be explained by a high priority of surgical cancer treatment at a time of reduced capacity for elective interventions.
The delayed decrease of radiotherapy-related hospitalizations might be a consequence of a curtailed oncological screening for CC relation to the pandemic. This reasoning would entail the presumption of a lag between the initial diagnosis and initiation of treatment of several weeks. As an alternative interpretation, these findings might be a consequence of intended treatment postponements. However, few radiation oncology institutes in Germany reported a postponement of treatment as a consequence of the pandemic [7]. From an outcome perspective, there exist no valid data on the effects of a delayed treatment in CC [24].
In contrast to other countries [25], there was no official suspension of CC screening during the corona lockdown in Germany. However, out of fear and because of the call to reduce contacts, women might have abstained from screening during this period. Such a reduced willingness might have detrimental effects on patients and treatment success [26]. This is in line with data based on German practices where, among other disciplines, gynecology practices showed a strong reduction in case numbers by 21.7 to 30.8% between March and May 2020, [27]. Another analysis based on the same data source as our study but addressing inpatient admissions in general, found that the decline in case numbers started immediately after introduction of the lockdown restrictions [13].
In contrast, for HNC, a significant increase in performed radiotherapeutic fractions was observed in our cohort in 2020 in the 20 weeks following the lockdown announcement on March 16, 2020, as well as in the 13-week period from May 4, 2020 onwards, in comparison with the average of the two previous years. In our analysis of related inpatient hospital admissions, an increase could be observed for admissions in which radiotherapeutic procedures were performed, whereas no differences could be observed for radiotherapeutic admissions with additional chemotherapy.
The increase in case numbers and fractions found in HNC was accompanied by a numerical decrease in cases with surgery, which was, however, not statistically significant. Here, respective changes in radiotherapy occurred after initiation of the lockdown measures with a delay of 1 to 2 weeks only. This delay is explainable by radiotherapy planning prior to hospitalization. The shift in hospitalized cases might reflect a preference for non-surgical treatments during the lockdown. Such a reasoning might especially apply to head and neck cancer, where surgery is complex and imposes significant COVID-related risks for the surgical team [3, 26]. One guideline recommended such a temporary shift from surgery to radiotherapy during the onset of the pandemic [1]. In contrast to our findings, Spencer et al. found no relevant change in the number of courses and attendances in their study for HNC in the already mentioned British data [5]. However, due to the centralized and unified character of the British health care system in the form of the NHS, measures and guidelines might have been introduced more coherently and stringently. In addition, the British study encompassed in- and outpatient data, with only a few centers failing to provide data.
Apart from this shift, other factors might have contributed to this finding: university hospitals with their large capacities might have received more patients in the aftermath of the first wave of the pandemic; diagnoses might be delayed, resulting in more advanced cases with different treatment approaches. In addition, the proportion of cases treated in an in- or outpatient setting might have changed. This applies to CC (outpatient treatment preferred during/after the lockdown) and HNC (inpatient treatment preferred during/after the lockdown). Finally, alternating chemotherapy regimens might have contributed to a change in admissions and fractions administered during hospitalization.
In a survey performed among radiation oncologists in Germany, Austria, and Switzerland, most of the radiation oncology institutes (ROIs) reported no change in curative or palliative treatment [7]. Fractionation schedules were changed in 25.7% (curative radiotherapy) and 42.1% (palliative radiotherapy) of the ROIs, while the general postponement of treatment played virtually no role. The authors also found that non-university ROIs were more willing to change their treatment pattern. This might well apply to our setting, which addressed only university institutions. The decrease in case numbers in the survey was independent of the regional incidence of COVID-19 and the type of institute (university vs. non-university).
Limitations
The major limitation of the present analysis lies in the selective consideration of inpatients. However, radiotherapy might have shifted from an in- to an outpatient setting in the wake of the lockdown. We tried to mitigate this effect by focusing on entities with a strong inpatient component of treatment such as the regular use of concomitant radiochemotherapy. In addition, as the lockdown restrictions specifically targeted the inpatient setting while sparing outpatient cancer treatment and screening, a shift from in- to outpatient treatment would still in part be detectable in the hospital setting.
Regarding the observational unit of cases, confounded results might occur if shorter but repeated hospitalizations became the preferred pattern during the lockdown. However, such an alteration appears unlikely, as it would contradict the lockdown restrictions calling for reduced hospitalizations [19]. Thus, for assessment of temporal changes in radiotherapy, fractions are a more reliable endpoint than cases.
Furthermore, we have no detailed information on fractionation or dose concepts. In order to shorten treatments, hypofractionated or even ultra-hypofractionated radiotherapy might have become a frequently applied regime. An increased use of such ultra-hypofractionated concepts was especially striking in British data and the treatment of breast cancer [5]. The German Radiation Oncology Society (Deutsche Gesellschaft für Radioonkologie, DEGRO) recommended the application of hypofractionated concepts in order to reduce treatment time [28]. Two sources of alternated fractionation play an important role in HNC. On the one hand there might be a decrease in hyperfractionated concepts and an increase in the frequency of hypofractionation [18]. However, if such alterations were apparent in our data, we would underestimate the lockdown effect in terms of radiotherapy use, where we observed increased numbers during the lockdown period.
Admission varied considerably between institutions, decreasing the power to detect possible alterations caused by the lockdown. By applying mixed models, we could reduce the statistical variation between considered hospitals and estimate a generalized effect.
Another limitation may be the overlapping of cases between some therapy categories (Supplementary Table S1). For example, for CC, some cases of the category “radiotherapy without surgery, chemotherapy present” may also be included in the group “radiotherapy without surgery without brachytherapy.” However, we chose this approach to look at possible effects from different perspectives by analyzing the subgroups. Furthermore, the therapy category “surgery present” might include both “pure” surgical cases and those with additional radiochemotherapy during the same hospital stay. Although we assume that the latter is rather a minority, future analyses may aim at a stricter and more finely granulated separation between these therapy categories.
Further limitations introduced by the use of the claims dataset were also described in more detail in [13].